Relationship of the eye uptake of N-isopropyl-p-(/sup 123/I)iodoamphetamine to melanin production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holman, B.L.; Wick, M.M.; Kaplan, M.L.

1984-03-01

Eye uptake has been a potential concern with N-isopropyl-p-(/sup 123/I)iodoamphetamine (I-123 IMP) because it has been observed in certain animal species. The authors have investigated the cause of the eye uptake and its relationship to melanin synthesis. In a 1-yr-old cynomolgus monkey, high concentration of the tracer was seen in the eyes regardless of the type of anesthesia (pentobarbital or ketamine) or the oral administration of Lugol's solution. The eye uptake at 24 hr after injection of I-123 IMP was equally high in an 8-yr-old rhesus monkey. The ratio of radioactivity in the eye of black compared with white albinomore » mice was 10:1 at 30 min, 18:1 at 2 hr and 36:1 at 24 hr after injection if I-123 IMP. No eye uptake above soft-tissue background was seen in five patients at 2, 24, and 48 hr after injection. I-123 IMP is avidly incorporated into melanocytes actively producing melanin, but substantially less in melanocytes where production of melanin has ceased as in the human eye.« less

Kinetic analysis of IMP split dose method for two consecutive measurement of cerebral blood flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishizawa, S.; Yonekura, Y.; Tanaka, F.

1994-05-01

The split dose method for two consecutive measurements of cerebral blood flow (CBF) with I-123 IMP seems to offer a great merit to the SPECT study of the brain. However, because of complexity of the dynamics of IMP, it is not clear if microsphere (MS) model permits a estimation of CBF for the 2nd dose. We applied kinetic (KN) analysis based on 2 compartment model to the dynamic SPECT scan data, and compared the results with those obtained by MS model. Dynamic SPECT (1-min scans for 50 min) was performed using 3-head SPECT camera in 5 patients to test themore » reproducibility of measured CBF and in 9 patients to test the vascular response to acetazolamide (ACZ). Two doses of IMP (111 MBq each) were injected at the time of, and 25 min after, the scan initiation. ACZ (1g) was administered at 13 min. Arterial blood samples were drawn manually during the scan and an octanol extracted input function was obtained. Dynamic scan data for 22 min was used for CBF by KN analysis (K1), and 4-min scan data at 5 min for CBF by MS model (Km), for each dose. For 2nd CBF by MS model, simple subtraction of brain activity due to the I st dose was done using 4-min scan data just prior to the 2nd dose. Reproducibility of measured CBF by KN analysis was excellent (r=0.949, 1st K1=39.2{plus_minus}5.6 and 2nd K1=38.5{plus_minus}6.6 ml/l00g/min: mean{plus_minus}SD). Vascular response to ACZ was good (1st K1=42.4{plus_minus}7.8 to 2nd K1=67.9{plus_minus}10.0) in areas without ischemia, but poor (1st K1=41.1{plus_minus}8.5 to 2nd K1=46.1{plus_minus}11.1) in ischemic areas. Compared to KN analysis, MS model underestimated 3.5% for the 1st CBF measurement and 12.8% for the 2nd. However, excellent correlation was observed not only between 1st K1 and Km (r=0.993, slope=0.920) but between 2nd K1 and Km (r=0.994, slope=0.814), and the results permitted a reasonable correction for Km.« less

CT-based attenuation correction and resolution compensation for I-123 IMP brain SPECT normal database: a multicenter phantom study.

PubMed

Inui, Yoshitaka; Ichihara, Takashi; Uno, Masaki; Ishiguro, Masanobu; Ito, Kengo; Kato, Katsuhiko; Sakuma, Hajime; Okazawa, Hidehiko; Toyama, Hiroshi

2018-06-01

Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings. The proposed acquisition and processing protocols were those routinely used at each participating center with additional triple energy window (TEW) scatter correction (SC) and computed tomography (CT) based attenuation correction (CTAC). A multicenter phantom study was conducted on six imaging systems in five centers, with either single photon emission computed tomography (SPECT) or SPECT/CT, and two brain phantoms. The gray/white matter I-123 activity ratio in the brain phantoms was 4, and they were enclosed in either an artificial adult male skull, 1300 Hounsfield units (HU), a female skull, 850 HU, or an acrylic cover. The cut-off frequency of the Butterworth filters was adjusted so that the spatial resolution was unified to a 17.9 mm full width at half maximum (FWHM), that of the lowest resolution system. The gray-to-white matter count ratios were measured from SPECT images and compared with the actual activity ratio. In addition, mean, standard deviation and coefficient of variation images were calculated after normalization and anatomical standardization to evaluate the variability of the NDB. The gray-to-white matter count ratio error without SC and attenuation correction (AC) was significantly larger for higher bone densities (p < 0.05). The count ratio error with TEW and CTAC was approximately 5% regardless of bone density. After adjustment of the spatial resolution in the SPECT images, the variability of the NDB decreased and was comparable to that of the NDB without correction. The proposed protocol showed potential for constructing an appropriate common NDB from SPECT images with SC, AC and spatial resolution compensation.

Hemimegalencephaly: Clinical, EEG, neuroimaging, and IMP-SPECT correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konkol, R.J.; Maister, B.H.; Wells, R.G.

1990-11-01

Iofetamine-single photon emission computed tomography (IMP-SPECT) was performed on 2 girls (5 1/2 and 6 years of age) with histories of intractable seizures, developmental delay, and unilateral hemiparesis secondary to hemimegalencephaly. Electroencephalography (EEG) revealed frequent focal discharges in 1 patient, while a nearly continuous burst suppression pattern over the malformed hemisphere was recorded in the other. IMP-SPECT demonstrated a good correlation with neuroimaging studies. In spite of the different EEG patterns, which had been proposed to predict contrasting clinical outcomes, both IMP-SPECT scans disclosed a similar decrease in tracer uptake in the malformed hemisphere. These results are consistent with themore » pattern of decreased tracer uptake found in other interictal studies of focal seizures without cerebral malformations. In view of recent recommendations for hemispherectomy in these patients, we suggest that the IMP-SPECT scan be used to compliment EEG as a method to define the extent of abnormality which may be more relevant to long-term prognosis than EEG alone.« less

Efficacy of superficial temporal artery-middle cerebral artery double anastomoses in a patient with rapidly progressive moyamoya disease: case report.

PubMed

Yokosawa, Michiko; Hayashi, Toshiaki; Shirane, Reizo; Tominaga, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction.

Efficacy of Superficial Temporal Artery-Middle Cerebral Artery Double Anastomoses in a Patient with Rapidly Progressive Moyamoya Disease: Case Report

PubMed Central

YOKOSAWA, Michiko; HAYASHI, Toshiaki; SHIRANE, Reizo; TOMINAGA, Teiji

2014-01-01

Moyamoya disease can be associated with a rapidly progressive course in young patients. This report describes a patient with moyamoya disease who experienced rapid disease progression, resulting in cerebral infarction and a wide area of diminished cerebral perfusion. Double superficial temporal artery (STA)-middle cerebral artery (MCA) anastomoses were utilized to immediately increase cerebral perfusion in the affected area. This case involved a 5-year-old girl who had been diagnosed with moyamoya disease and had undergone STA-MCA anastomosis with indirect bypass in the right hemisphere at the age of 3. At the time of presentation, magnetic resonance (MR) imaging showed cerebral infarction at the left frontal lobe, and MR angiography showed rapidly progressive narrowing of the left MCA that had not been present 3 months prior. N-isopropyl-p-[I123] iodoamphetamine single-photon emission computed tomography (IMP-SPECT) showed markedly decreased uptake in the left hemisphere. She underwent emergent STA-MCA double anastomoses with indirect bypass on the left side. IMP-SPECT showed marked increase in uptake in the left hemisphere. The anterior cerebral artery (ACA) territory adjacent to the cerebral infarction also showed increased uptake on the SPECT. Postoperatively, there were no clinical or radiographic indications of ischemic or hemorrhagic complications. Double anastomoses are effective in quickly and significantly increasing blood flow. The postoperative course in this case was uneventful. Double anastomoses are a surgical option for patients with moyamoya disease who show rapid disease progression, even in those in the acute phase of cerebral infarction. PMID:24584280

Dual-radiotracer translational SPECT neuroimaging. Comparison of three methods for the simultaneous brain imaging of D2/3 and 5-HT2A receptors.

PubMed

Tsartsalis, Stergios; Tournier, Benjamin B; Habiby, Selim; Ben Hamadi, Meriem; Barca, Cristina; Ginovart, Nathalie; Millet, Philippe

2018-04-30

SPECT imaging with two radiotracers at the same time is feasible if two different radioisotopes are employed, given their distinct energy emission spectra. In the case of 123 I and 125 I, dual SPECT imaging is not straightforward: 123 I emits photons at a principal energy emission spectrum of 143.1-179.9 keV. However, it also emits at a secondary energy spectrum (15-45 keV) that overlaps with the one of 125 I and the resulting cross-talk of emissions impedes the accurate quantification of 125 I. In this paper, we describe three different methods for the correction of this cross-talk and the simultaneous in vivo [ 123 I]IBZM and [ 125 I]R91150 imaging of D 2/3 and 5-HT 2A receptors in the rat brain. Three methods were evaluated for the correction of the effect of cross-talk in a series of simultaneous, [ 123 I]IBZM and [ 125 I]R91150 in vivo and phantom SPECT scans. Method 1 employs a dual-energy window (DEW) approach, in which the cross-talk on 125 I is considered a stable fraction of the energy emitted from 123 I at the principal emission spectrum. The coefficient describing the relationship between the emission of 123 I at the principal and the secondary spectrum was estimated from a series of single-radiotracer [ 123 I]IBZM SPECT studies. In Method 2, spectral factor analysis (FA) is applied to separate the radioactivity from 123 I and 125 I on the basis of their distinct emission patterns across the energy spectrum. Method 3 uses a modified simplified reference tissue model (SRTM C ) to describe the kinetics of [ 125 I]R91150. It includes the coefficient describing the cross-talk on 125 I from 123 I in the model parameters. The results of the correction of cross-talk on [ 125 I]R91150 binding potential (BP ND ) with each of the three methods, using cerebellum as the reference region, were validated against the results of a series of single-radiotracer [ 123 I]R91150 SPECT studies. In addition, the DEW approach (Method 1), considered to be the most straightforward to apply of the three, was further applied in a dual-radiotracer SPECT study of the relationship between D 2/3 and 5-HT 2A receptor binding in the striatum, both at the voxel and at the regional level. Average regional BP ND values of [ 125 I]R91150, estimated on the cross-talk corrected dual-radiotracer SPECT studies provided satisfactory correlations with the BP ND values for [ 123 I]R91150 from single-radiotracer studies: r = 0.92, p < 0.001 for Method 1, r = 0.92, p < 0.001 for Method 2, r = 0.92, p < 0.001, for Method 3. The coefficient describing the ratio of the 123 I-emitted radioactivity at the 125 I-emission spectrum to the radioactivity that it emits at its principal emission spectrum was 0.34 in vivo. Dual-radiotracer in vivo SPECT studies corrected with Method 1 demonstrated a positive correlation between D 2/3 and 5-HT 2A receptor binding in the rat nucleus accumbens at the voxel level. At the VOI-level, a positive correlation was confirmed in the same region (r = 0.78, p < 0.01). Dual-radiotracer SPECT imaging using 123 I and 125 I-labeled radiotracers is feasible if the cross-talk of 123 I on the 125 I emission spectrum is properly corrected. The most straightforward approach is Method 1, in which a fraction (34%) of the radioactivity emitted from 123 I at its principal energy spectrum is subtracted from the measured radioactivity at the spectrum of 125 I. With this method, a positive correlation between the binding of [ 123 I]IBZM and [ 125 I]R91150 was demonstrated in the rat nucleus accumbens. This result highlights the interest of dual-radiotracer SPECT imaging to study multiple neurotransmitter systems at the same time and under the same biological conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Does preoperative measurement of cerebral blood flow with acetazolamide challenge in addition to preoperative measurement of cerebral blood flow at the resting state increase the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy? Results from 500 cases with brain perfusion single-photon emission computed tomography study.

PubMed

Oshida, Sotaro; Ogasawara, Kuniaki; Saura, Hiroaki; Yoshida, Koji; Fujiwara, Shunro; Kojima, Daigo; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

2015-01-01

The purpose of the present study was to determine whether preoperative measurement of cerebral blood flow (CBF) with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy (CEA). CBF at the resting state and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively assessed using N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-autoradiography method with single-photon emission computed tomography (SPECT) before CEA in 500 patients with ipsilateral internal carotid artery stenosis (≥ 70%). CBF measurement using (123)I-IMP SPECT was also performed immediately and 3 days after CEA. A region of interest (ROI) was automatically placed in the middle cerebral artery territory in the affected cerebral hemisphere using a three-dimensional stereotactic ROI template. Preoperative decreases in CBF at the resting state [95% confidence intervals (CIs), 0.855 to 0.967; P = 0.0023] and preoperative decreases in CVR to acetazolamide (95% CIs, 0.844 to 0.912; P < 0.0001) were significant independent predictors of post-CEA hyperperfusion. The area under the receiver operating characteristic curve for prediction of the development of post-CEA hyperperfusion was significantly greater for CVR to acetazolamide than for CBF at the resting state (difference between areas, 0.173; P < 0.0001). Sensitivity, specificity, and positive- and negative-predictive values for the prediction of the development of post-CEA hyperperfusion were significantly greater for CVR to acetazolamide than for CBF at the resting state (P < 0.05, respectively). The present study demonstrated that preoperative measurement of CBF with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of the development of post-CEA hyperperfusion.

[Development of a Striatal and Skull Phantom for Quantitative 123I-FP-CIT SPECT].

PubMed

Ishiguro, Masanobu; Uno, Masaki; Miyazaki, Takuma; Kataoka, Yumi; Toyama, Hiroshi; Ichihara, Takashi

123 Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 123 I-FP-CIT) single photon emission computerized tomography (SPECT) images are used for differential diagnosis such as Parkinson's disease (PD). Specific binding ratio (SBR) is affected by scattering and attenuation in SPECT imaging, because gender and age lead to changes in skull density. It is necessary to clarify and correct the influence of the phantom simulating the the skull. The purpose of this study was to develop phantoms that can evaluate scattering and attenuation correction. Skull phantoms were prepared based on the measuring the results of the average computed tomography (CT) value, average skull thickness of 12 males and 16 females. 123 I-FP-CIT SPECT imaging of striatal phantom was performed with these skull phantoms, which reproduced normal and PD. SPECT images, were reconstructed with scattering and attenuation correction. SBR with partial volume effect corrected (SBR act ) and conventional SBR (SBR Bolt ) were measured and compared. The striatum and the skull phantoms along with 123 I-FP-CIT were able to reproduce the normal accumulation and disease state of PD and further those reproduced the influence of skull density on SPECT imaging. The error rate with the true SBR, SBR act was much smaller than SBR Bolt . The effect on SBR could be corrected by scattering and attenuation correction even if the skull density changes with 123 I-FP-CIT on SPECT imaging. The combination of triple energy window method and CT-attenuation correction method would be the best correction method for SBR act .

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

A case of Cotard syndrome: (123)I-IBZM SPECT imaging of striatal D(2) receptor binding.

PubMed

De Risio, Sergio; De Rossi, Giuseppe; Sarchiapone, Marco; Camardese, Giovanni; Carli, Vladimir; Cuomo, Chiara; Satta, Maria Antonietta; Di Giuda, Daniela

2004-01-15

A case of 'dèlire de nègation' that suddenly appeared in a 43-year-old male is presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO-SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2) receptor binding that further decreased after treatment.

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

PubMed

Miyamoto, T; Horigome, H; Sato, H; Yamada, M; Inai, K; Takeda, T; Ishikawa, N; Hoshino, H; Itai, Y

1996-02-01

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

Combined visual and semi-quantitative assessment of 123I-FP-CIT SPECT for the diagnosis of dopaminergic neurodegenerative diseases.

PubMed

Ueda, Jun; Yoshimura, Hajime; Shimizu, Keiji; Hino, Megumu; Kohara, Nobuo

2017-07-01

Visual and semi-quantitative assessments of 123 I-FP-CIT single-photon emission computed tomography (SPECT) are useful for the diagnosis of dopaminergic neurodegenerative diseases (dNDD), including Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. However, the diagnostic value of combined visual and semi-quantitative assessment in dNDD remains unclear. Among 239 consecutive patients with a newly diagnosed possible parkinsonian syndrome who underwent 123 I-FP-CIT SPECT in our medical center, 114 patients with a disease duration less than 7 years were diagnosed as dNDD with the established criteria or as non-dNDD according to clinical judgment. We retrospectively examined their clinical characteristics and visual and semi-quantitative assessments of 123 I-FP-CIT SPECT. The striatal binding ratio (SBR) was used as a semi-quantitative measure of 123 I-FP-CIT SPECT. We calculated the sensitivity and specificity of visual assessment alone, semi-quantitative assessment alone, and combined visual and semi-quantitative assessment for the diagnosis of dNDD. SBR was correlated with visual assessment. Some dNDD patients with a normal visual assessment had an abnormal SBR, and vice versa. There was no statistically significant difference between sensitivity of the diagnosis with visual assessment alone and semi-quantitative assessment alone (91.2 vs. 86.8%, respectively, p = 0.29). Combined visual and semi-quantitative assessment demonstrated superior sensitivity (96.7%) to visual assessment (p = 0.03) or semi-quantitative assessment (p = 0.003) alone with equal specificity. Visual and semi-quantitative assessments of 123 I-FP-CIT SPECT are helpful for the diagnosis of dNDD, and combined visual and semi-quantitative assessment shows superior sensitivity with equal specificity.

Clinical results with beta-methyl-p-(123I)iodophenylpentadecanoic acid, single-photon emission computed tomography in cardiac disease.

PubMed

Nishimura, T; Uehara, T; Shimonagata, T; Nagata, S; Haze, K

1994-01-01

This study was undertaken to evaluate the relationships, between myocardial perfusion and metabolism. Simultaneous beta-methyl-p(123I)iodophenylpentadecanoic acid (123I-BMIPP) and thallium 201 myocardial single-photon emission computed tomography (SPECT) were performed in 25 patients with myocardial infarction (group A) and 16 patients with hypertrophic cardiomyopathy (group B). The severity scores of 123I-BMIPP and 201Tl myocardial SPECT images were evaluated semiquantitatively by segmental analysis. In Group A, dissociations between thallium- and 123I-BMIPP-imaged defects were frequently observed in patients with successful reperfusion compared with those with no reperfusion and those with reinfarction. In four patients with successful reperfusion, repeated 123I-BMIPP and 201Tl myocardial SPECT showed gradual improvement of the 123I-BMIPP severity score compared with the thallium severity score. In group B, dissociations between thallium- and 123I-BMIPP-imaged defects were also demonstrated in hypertrophic myocardium. In addition, nonhypertrophic myocardium also had decreased 123I-BMIPP uptake. In groups A and B, 123I-BMIPP severity scores correlated well with left ventricular function compared with thallium severity scores. These findings indicate that 123I-BMIPP is a suitable agent for the assessment of functional integrity, because left ventricular wall motion is energy dependent and 123I-BMIPP may reflect an aspect of myocardial energy production. This agent may be useful for the early detection and patient management of various heart diseases as an alternative to positron emission tomographic study.

Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors.

PubMed

Kobayashi, Masato; Matsunari, Ichiro; Nishi, Kodai; Mizutani, Asuka; Miyazaki, Yoshiharu; Ogai, Kazuhiro; Sugama, Jyunko; Shiba, Kazuhiro; Kawai, Keiichi; Kinuya, Seigo

2016-05-01

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors. 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT. The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection. Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

Muscarinic cholinergic receptor binding: in vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drayer, B.; Jaszczak, R.; Coleman, E.

1982-06-01

An attempt was made to characterize, in vivo, specific binding to the muscarinic cholinergic receptor in the calf using the radioiodinated ligand quinuclidinyl benzilate (/sup 123/I-OH-QNB) and single photon detection emission computed tomography (SPECT). The supratentorial brain activity was significantly increased after the intravenous infusion of /sup 123/I-OH-QNB as compared to free /sup 123/I. Scopolamine, a muscarinic cholinergic receptor antagonist, decreased the measured brain activity when infused prior to /sup 123/I-OH-QNB consistent with pharmacologic blockade of specific receptor binding. Quantitative in vitro tissue distribution studies obtained following SPECT imaging were consistent with regionally distinct specific receptor binding in the striatummore » and cortical gray matter, nonspecific binding in the cerebellum, and pharmacologic blockade of specific binding sites with scopolamine. Although /sup 123/I-OH-QNB is not the ideal radioligand, our limited success will hopefully encourage the development of improved binding probes for SPECT imaging and quantitation.« less

Myocardial scintigraphy using a fatty acid analogue detects coronary artery disease in hemodialysis patients.

PubMed

Nishimura, Masato; Hashimoto, Tetsuya; Kobayashi, Hiroyuki; Fukuda, Toyofumi; Okino, Koji; Yamamoto, Noriyuki; Fujita, Hiroshi; Inoue Tsunehiko Nishimura, Naoto; Ono, Toshihiko

2004-08-01

Coronary artery disease contributes significantly to mortality in end-stage renal disease (ESRD) patients. Single-photon emission computed tomography (SPECT) using an iodinated fatty acid analogue, iodine-123-methyl iodophenylpentadecanoic acid (123I-BMIPP), can assess fatty acid metabolism in the myocardium. We investigated the ability of 123I-BMIPP SPECT to detect coronary artery disease in hemodialysis patients compared with 201thallium chloride (201Tl) SPECT. We prospectively studied 130 ESRD patients undergoing hemodialysis for a mean of 88.6 months (male/female, 77/53; mean age, 63.8 years). Dual SPECT using 123I-BMIPP and 201Tl was performed, followed by coronary angiography. SPECT findings were graded in 17 segments on a five-point scale (0, normal uptake; 4, none) and assessed as a summed score. By coronary angiography, 71.5% of patients (93/130) had significant coronary stenosis (> or =75%), and five patients showed coronary spasm without coronary stenosis. When a BMIPP summed score of 6 or more was defined as abnormal, sensitivity, specificity, and accuracy for detecting coronary artery disease by BMIPP SPECT were 98.0%, 65.6%, and 90.0%, respectively; in contrast, these parameters for detecting coronary artery disease by Tl SPECT were 84.7%, 46.9%, and 75.0%, respectively, when a Tl summed score of 1 or more was defined as abnormal. In receiver operating characteristic analysis, the area under the curve was 0.895 in BMIPP and 0.727 in Tl SPECT, respectively. Resting BMIPP SPECT is superior to Tl SPECT for detecting coronary lesions, and provides safe screening for coronary artery disease among maintenance hemodialysis patients.

A novel computer-assisted image analysis of [123I]β-CIT SPECT images improves the diagnostic accuracy of parkinsonian disorders.

PubMed

Goebel, Georg; Seppi, Klaus; Donnemiller, Eveline; Warwitz, Boris; Wenning, Gregor K; Virgolini, Irene; Poewe, Werner; Scherfler, Christoph

2011-04-01

The purpose of this study was to develop an observer-independent algorithm for the correct classification of dopamine transporter SPECT images as Parkinson's disease (PD), multiple system atrophy parkinson variant (MSA-P), progressive supranuclear palsy (PSP) or normal. A total of 60 subjects with clinically probable PD (n = 15), MSA-P (n = 15) and PSP (n = 15), and 15 age-matched healthy volunteers, were studied with the dopamine transporter ligand [(123)I]β-CIT. Parametric images of the specific-to-nondisplaceable equilibrium partition coefficient (BP(ND)) were generated. Following a voxel-wise ANOVA, cut-off values were calculated from the voxel values of the resulting six post-hoc t-test maps. The percentages of the volume of an individual BP(ND) image remaining below and above the cut-off values were determined. The higher percentage of image volume from all six cut-off matrices was used to classify an individual's image. For validation, the algorithm was compared to a conventional region of interest analysis. The predictive diagnostic accuracy of the algorithm in the correct assignment of a [(123)I]β-CIT SPECT image was 83.3% and increased to 93.3% on merging the MSA-P and PSP groups. In contrast the multinomial logistic regression of mean region of interest values of the caudate, putamen and midbrain revealed a diagnostic accuracy of 71.7%. In contrast to a rater-driven approach, this novel method was superior in classifying [(123)I]β-CIT-SPECT images as one of four diagnostic entities. In combination with the investigator-driven visual assessment of SPECT images, this clinical decision support tool would help to improve the diagnostic yield of [(123)I]β-CIT SPECT in patients presenting with parkinsonism at their initial visit.

Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single photon emission computed tomography in Lewy body diseases: complementary or alternative techniques?

PubMed

Treglia, Giorgio; Cason, Ernesto; Cortelli, Pietro; Gabellini, Anna; Liguori, Rocco; Bagnato, Antonio; Giordano, Alessandro; Fagioli, Giorgio

2014-01-01

To compare myocardial sympathetic imaging using (123)I-Metaiodobenzylguanidine (MIBG) scintigraphy and striatal dopaminergic imaging using (123)I-Ioflupane (FP-CIT) single photon emission computed tomography (SPECT) in patients with suspected Lewy body diseases (LBD). Ninety-nine patients who performed both methods within 2 months for differential diagnosis between Parkinson's disease (PD) and other parkinsonism (n = 68) or between dementia with Lewy bodies (DLB) and other dementia (n = 31) were enrolled. Sensitivity, specificity, accuracy, positive and negative predictive values of both methods were calculated. For (123) I-MIBG scintigraphy, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 83%, 79%, 82%, 86%, and 76%, respectively. For (123)I-FP-CIT SPECT, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 93%, 41%, 73%, 71%, and 80%, respectively. There was a statistically significant difference between these two methods in patients without LBD, but not in patients with LBD. LBD usually present both myocardial sympathetic and striatal dopaminergic impairments. (123)I-FP-CIT SPECT presents high sensitivity in the diagnosis of LBD; (123)I-MIBG scintigraphy may have a complementary role in differential diagnosis between PD and other parkinsonism. These scintigraphic methods showed similar diagnostic accuracy in differential diagnosis between DLB and other dementia. Copyright © 2012 by the American Society of Neuroimaging.

Development of Realistic Striatal Digital Brain (SDB) Phantom for 123I-FP-CIT SPECT and Effect on Ventricle in the Brain for Semi-quantitative Index of Specific Binding Ratio.

PubMed

Furuta, Akihiro; Onishi, Hideo; Nakamoto, Kenta

This study aimed at developing the realistic striatal digital brain (SDB) phantom and to assess specific binding ratio (SBR) for ventricular effect in the 123 I-FP-CIT SPECT imaging. SDB phantom was constructed in to four segments (striatum, ventricle, brain parenchyma, and skull bone) using Percentile method and other image processing in the T2-weighted MR images. The reference image was converted into 128×128 matrixes to align MR images with SPECT images. The process image was reconstructed with projection data sets generated from reference images additive blurring, attenuation, scatter, and statically noise. The SDB phantom was evaluated to find the accuracy of calculated SBR and to find the effect of SBR with/without ventricular counts with the reference and process images. We developed and investigated the utility of the SDB phantom in the 123 I-FP-CIT SPECT clinical study. The true value of SBR was just marched to calculate SBR from reference and process images. The SBR was underestimated 58.0% with ventricular counts in reference image, however, was underestimated 162% with ventricular counts in process images. The SDB phantom provides an extremely convenient tool for discovering basic properties of 123 I-FP-CIT SPECT clinical study image. It was suggested that the SBR was susceptible to ventricle.

SPECT-evaluation of the monoamine uptake site ligand [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) in untreated patients with suspicion of Parkinson disease.

PubMed

Eising, E G; Müller, T T; Zander, C; Kuhn, W; Farahati, J; Reiners, C; Coenen, H H

1997-10-01

For a few years, data on SPECT-imaging of dopamine transporters with the cocaine derivate [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I] beta-CIT) have been reported mostly in healthy subjects or animals. This study reflects our preliminary results with SPECT-imaging of dopamine transporters using the cocaine analogue 123-beta-CIT in patients with untreated (de novo) parkinsonism. In 33 patients with clinical suspicion of Parkinson disease and 5 healthy controls, SPECT-imaging of dopamine transporters was performed 1, 4, and 24 hours after injection of 180 MBq of 123I-beta-CIT, which was generated by iododestannylation. None of the patients or controls had been treated before with neuroleptical drugs or any other pharmaceuticals with known binding to the dopamine transporters. Clinical symptoms were staged by the scales Hoehn-Yahr (HYS), Unified Parkinson Disease Rating Scale (UPDRS), and the self-rating scale of Beck depression inventory (BDI). For evaluation, striatal/cerebellar ratios were calculated to every time point. Significant correlations of 123I-beta-CIT uptake could be stated compared to UPDRS, HYS, and BDI values (Spearman correlation, p < 0.05). The symptoms of rigor and akinesia showed a significant correlation with the beta-CIT uptake, whereas the symptom of tremor failed, which may be caused by the location of tremor symptoms out of the striatum. Comparing the controls, a significant (p < 0.01) decrease of tracer uptake in parkinsonian patients is stated on the images at 24 hours p.i. In our patients, tracer uptake does not depend significantly on duration of disease and age. 123I-beta-CIT seems to be a promising tool in imaging of untreated parkinsonian patient.

Optimization of a simultaneous dual-isotope 201Tl/123I-MIBG myocardial SPECT imaging protocol with a CZT camera for trigger zone assessment after myocardial infarction for routine clinical settings: Are delayed acquisition and scatter correction necessary?

PubMed

D'estanque, Emmanuel; Hedon, Christophe; Lattuca, Benoît; Bourdon, Aurélie; Benkiran, Meriem; Verd, Aurélie; Roubille, François; Mariano-Goulart, Denis

2017-08-01

Dual-isotope 201 Tl/ 123 I-MIBG SPECT can assess trigger zones (dysfunctions in the autonomic nervous system located in areas of viable myocardium) that are substrate for ventricular arrhythmias after STEMI. This study evaluated the necessity of delayed acquisition and scatter correction for dual-isotope 201 Tl/ 123 I-MIBG SPECT studies with a CZT camera to identify trigger zones after revascularization in patients with STEMI in routine clinical settings. Sixty-nine patients were prospectively enrolled after revascularization to undergo 201 Tl/ 123 I-MIBG SPECT using a CZT camera (Discovery NM 530c, GE). The first acquisition was a single thallium study (before MIBG administration); the second and the third were early and late dual-isotope studies. We compared the scatter-uncorrected and scatter-corrected (TEW method) thallium studies with the results of magnetic resonance imaging or transthoracic echography (reference standard) to diagnose myocardial necrosis. Summed rest scores (SRS) were significantly higher in the delayed MIBG studies than the early MIBG studies. SRS and necrosis surface were significantly higher in the delayed thallium studies with scatter correction than without scatter correction, leading to less trigger zone diagnosis for the scatter-corrected studies. Compared with the scatter-uncorrected studies, the late thallium scatter-corrected studies provided the best diagnostic values for myocardial necrosis assessment. Delayed acquisitions and scatter-corrected dual-isotope 201 Tl/ 123 I-MIBG SPECT acquisitions provide an improved evaluation of trigger zones in routine clinical settings after revascularization for STEMI.

Prognostic study of cardiac events in Japanese high risk hemodialysis patients using I-BMIPP-SPECT: B-SAFE study design.

PubMed

Hasebe, Naoyuki; Moroi, Masao; Nishimura, Masato; Hara, Kazuhiro; Hase, Hiroki; Hashimoto, Akiyoshi; Kumita, Shinichiro; Haze, Kazuo; Momose, Mitsuru; Nagai, Yoji; Sugimoto, Tokuichiro; Kusano, Eiji; Akiba, Takashi; Nakata, Tomoaki; Nishimura, Tsunehiko; Tamaki, Nagara; Kikuchi, Kenjiro

2008-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in patients undergoing hemodialysis. Such patients frequently develop complications such as asymptomatic coronary artery disease (CAD). Accordingly, CAD must ideally be diagnosed at an early stage to improve prognosis. Although myocardial perfusion single photon emission computed tomography (SPECT) is valuable for diagnosing CAD, the stress test is not always applicable to patients on hemodialysis. Thus, we proposed a multicenter, prospective cohort study called "B-SAFE" to investigate the applicability of resting (123)I-labeled beta-methyl-iodophenylpentadecanoic acid ((123)I-BMIPP)-SPECT will be used to diagnose cardiac disease and evaluate the prognosis of hemodialysis patients by imaging myocardial fatty acid metabolism. B-SAFE began enrolling patients from June 2006 at 48 facilities. We performed (123)I-BMIPP-SPECT on 702 hemodialysis patients with risk factors for CAD until 30 November 2007 and plan to follow up for three years. The primary endpoints will be cardiac death and sudden death. This study should end in 2010.

Dynamic 123I-BMIPP single-photon emission computed tomography in patients with congestive heart failure: effect of angiotensin II type-1 receptor blockade.

PubMed

Takeishi, Yasuchika; Minamihaba, Osamu; Yamauchi, Sou; Arimoto, Takanori; Hirono, Osamu; Takahashi, Hiroki; Akiyama, Hideyuki; Miyamoto, Takuya; Nitobe, Joji; Nozaki, Naoki; Tachibana, Hidetada; Okuyama, Masaki; Fukui, Akio; Kubota, Isao; Okada, Akio; Takahashi, Kazuei

2004-04-01

Heart failure is a major and growing public health problem with a high mortality rate. Although recent studies have demonstrated that a variety of metabolic and/or neurohumoral factors are involved in the progression of this syndrome, the precise mechanisms responsible for this complex condition are poorly understood. To examine 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) kinetics in the early phase soon after tracer injection in patients with congestive heart failure (CHF), we performed dynamic single-photon emission computed tomography (SPECT). Twenty-six patients with CHF and eight control subjects were examined. The consecutive 15 images of 2-min dynamic SPECT were acquired for 30 min after injection. In the early phase after injection (0-4 min), a significant amount of radioactivity existed in the blood pool. After 6 min, the myocardial 123I-BMIPP image was clear and thus the washout rate of 123I-BMIPP from 6 to 30 min was calculated. The washout rate of 123I-BMIPP from the myocardium was faster in patients with CHF than in the controls (8 +/- 4 vs. -5 +/- 3%, p < 0.01). The washout rate of 123I-BMIPP demonstrated positive correlation with left ventricular (LV) end-diastolic volume index (R = 0.54, p < 0.02) and inverse correlation with LV ejection fraction (R = 0.53, p <0.02). Patients were given the angiotensin II type-1 receptor antagonist candesartan for 6 months, and dynamic SPECT was repeated. The enhanced washout rate of 123I-BMIPP in CHF was reduced after treatment with candesartan (p < 0.05). These data suggest that (1) enhanced washout of 123I-BMIPP was observed soon after injection in patients with CHF, (2) the activation of angiotensin II signaling pathway is involved as an intracellular mechanism for enhanced 123I-BMIPP washout in heart failure, and (3) improvement in fatty acid metabolism may represent a new mechanism for beneficial effects of angiotensin II receptor blockade on cardiac function and survival in patients with heart failure. 123I-BMIPP washout in the early phase obtained from dynamic SPECT may be a new marker for evaluating the severity of heart failure and the effects of medical treatment.

Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible.

PubMed

Booij, Jan; de Bruin, Kora; de Win, Maartje M L; Lavini, Cristina; den Heeten, Gerard J; Habraken, Jan B A

2003-08-01

A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand (123)I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [(123)I]FP-CIT binding ratios of the test/retest studies were 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [(123)I]FP-CIT binding ratios in rats is highly reproducible.

[123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography brain imaging in the diagnosis of dementia with Lewy bodies.

PubMed

Walker, Zuzana; Cummings, Jeffrey L

2012-01-01

Early, accurate diagnosis of dementia with Lewy bodies (DLB), in particular its differentiation from Alzheimer's disease, is important for optimal management, providing patients/carers with information about the likely symptomatology and illness course, allowing initiation of effective pharmacotherapy, and avoiding the consequences of neuroleptic sensitivity. Clinical diagnosis of DLB has high specificity but low sensitivity. Clinical trials of [(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography ([(123)I]FP-CIT SPECT) indicate high positive and negative percent agreement with reference to clinical diagnosis, and high sensitivity and specificity in patients with neuropathologically confirmed diagnoses of DLB. An abnormal [(123)I]FP-CIT SPECT image in patients fulfilling criteria for possible DLB advances the certainty of a diagnosis to probable DLB. [(123)I]FP-CIT SPECT, by identifying the striatal dopaminergic deficit, can be a valuable diagnostic aid and can provide support to a clinical diagnosis of DLB in patients with dementia. The technique is likely to be of particular utility in patients with dementia with an uncertain diagnosis. Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Dopamine transporter SPECT in patients with mitochondrial disorders

PubMed Central

Minnerop, M; Kornblum, C; Joe, A; Tatsch, K; Kunz, W; Klockgether, T; Wullner, U; Reinhardt, M

2005-01-01

Objective : To investigate the dopaminergic system in patients with known mitochondrial disorders and complex I deficiency. Methods: Dopamine transporter density was studied in 10 female patients with mitochondrial complex I deficiency by 123I-FP-CIT (N-ß-fluoropropyl-2ß-carbomethyl-3ß-(4-iodophenyl)-nortropane) SPECT. Results: No differences in 123I-FP-CIT striatal binding ratios were observed and no correlation of the degree of complex I deficiency and striatal binding ratios could be detected. Conclusions: These data argue against the possibility that mitochondrial complex I deficiency by itself is sufficient to elicit dopaminergic cell loss. PMID:15608010

Imaging of gene expression in live pancreatic islet cell lines using dual-isotope SPECT.

PubMed

Tai, Joo Ho; Nguyen, Binh; Wells, R Glenn; Kovacs, Michael S; McGirr, Rebecca; Prato, Frank S; Morgan, Timothy G; Dhanvantari, Savita

2008-01-01

We are combining nuclear medicine with molecular biology to establish a sensitive, quantitative, and tomographic method with which to detect gene expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to image multiple molecular events simultaneously, and coregistration of SPECT and CT images enables visualization of reporter gene expression in the correct anatomic context. We have engineered pancreatic islet cell lines for imaging with SPECT/CT after transplantation under the kidney capsule. INS-1 832/13 and alphaTC1-6 cells were stably transfected with a herpes simplex virus type 1-thymidine kinase-green fluorescent protein (HSV1-thymidine kinase-GFP) fusion construct (tkgfp). After clonal selection, radiolabel uptake was determined by incubation with 5-(131)I-iodo-1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)uracil ((131)I-FIAU) (alphaTC1-6 cells) or (123)I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after alphaTC1-6/tkgfp cells had been labeled with either (131)I-FIAU or (111)In-tropolone and transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT images were coregistered to CT. In a second study using simultaneous acquisition dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with (111)In-tropolone before transplantation. Mice were then systemically administered (123)I-FIAU and data for both (131)I and (111)In were acquired simultaneously. alphaTC1-6/tkgfp cells showed a 15-fold greater uptake of (131)I-FIAU, and INS-1/tkgfp cells showed a 12-fold greater uptake of (123)I-FIAU, compared with that of wild-type cells. After transplantation under the kidney capsule, both reporter gene expression and location of cells could be visualized in vivo with dual-isotope SPECT. Immunohistochemistry confirmed the presence of glucagon- and insulin-positive cells at the site of transplantation. Dual-isotope SPECT is a promising method to detect gene expression in and location of transplanted pancreatic cells in vivo.

Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

NASA Astrophysics Data System (ADS)

Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

2011-08-01

The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us to understand reliability of I-123 ADAM SPECT imaging and further develop new strategy for the treatment of psychiatric disorders.

Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following traumatic brain injury.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Kurokawa, Tetsu; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2010-10-01

We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [(123)I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI.

Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following traumatic brain injury

PubMed Central

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Kurokawa, Tetsu; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2010-01-01

We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [123I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [123I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI. PMID:20683454

A case of successful treatment with donepezil of olfactory hallucination in parkinson disease.

PubMed

Osada, Osamu; Iwasaki, Akira

2017-01-31

We report a 74-year-old female patient with Parkinson disease (PD). Around 2010, she developed depression and bradykinesia and was diagnosed as PD. In July 2014, she came to our hospital, of which she lived in the neighborhood. In the last part of December 2014, she felt uneasy about her fecal smell and saw a psychiatrist in the first part of January 2015. Quetiapine (25 mg/day) was added. In the last part of January, she complained of fecal smell everywhere and could not take a meal. No-one else could detect the smell. A diagnosis of olfactory hallucination was made. The next day after increasing to 75mg/day, however, she was admitted to our hospital because of refusing to take medicine. After introducing donepezil, olfactory hallucination subsided and her appetite was improved. Brain MRI showed atrophy of the bilateral temporal lobes and N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography ( 123 I-IMP-SPECT) revealed hypoperfusion in the bilateral mesial temporal lobes. We suppose that cholinergic denervation in the mesial temporal lobes is an important determinant of her olfactory hallucination.

123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility.

PubMed

Staley, Julie K; van Dyck, Christopher H; Weinzimmer, David; Brenner, Eric; Baldwin, Ronald M; Tamagnan, Gilles D; Riccardi, Patrizia; Mitsis, Effie; Seibyl, John P

2005-09-01

(123)I-5-IA-85380 ((123)I-5-IA; [(123)I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging beta(2)-containing nicotinic acetylcholine receptors (beta(2)-nAChRs) in brain. Beta(2)-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of (123)I-5-IA using SPECT in healthy nonsmokers was studied. Ten healthy nonsmokers (mean age +/- SD, 43.7 +/- 9.9 y) underwent two (123)I-5-IA SPECT scans within 4 wk. (123)I-5-IA was administered as a bolus (125.8 +/- 14.6 MBq) plus constant infusion (18.1 +/- 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10-14 h). The test-retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures V(T)' (ratio of total uptake to total plasma parent concentration) and V(T) (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum. Linear regression analysis revealed that time-activity curves for both plasma and brain (123)I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f(1)), total parent, and clearance demonstrated good test-retest variability (mean, 10.9%-12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test-retest variability (11.1%-16.4%) that improved when corrected for infusion rate (mean, 8.2%-9.9%) or for injected dose (mean, 9.5%-13.3%). V(T)' demonstrated better test-retest variability (mean, 7.0%-8.9%) than V(T) (mean, 12.9%-14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83-0.90) and %ID/mL (ICC = 0.93-0.96) compared with V(T)' (ICC = 0.30-0.64) and V(T) (ICC = 0.28-0.60). The lower reliability of V(T) was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68). These results support the feasibility and reproducibility of equilibrium imaging with (123)I-5-IA for measurement of beta(2)-nAChRs in human brain.

Early diagnosis of interferon-induced myocardial disorder in patients with chronic hepatitis C: evaluation by myocardial imaging with 123I-BMIPP.

PubMed

Kondo, Y; Yukinaka, M; Nomura, M; Nakaya, Y; Ito, S

2000-01-01

Interferon (IFN) therapy for chronic hepatitis C is sometimes associated with cardiac complications. In the present study, we performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) in order to evaluate myocardial disorders caused by IFN. We studied 40 healthy subjects (H group) and 25 patients with chronic hepatitis C who had been treated with IFN (IFN group). A Holter electrocardiogram (ECG) was performed and the autonomic nervous function was assessed by analyzing the spectral variability and 1/f fluctuation of heart rate. Myocardial planner imaging with 123I-BMIPP was performed to obtain the time activity curve for 20min immediately after administration of 123I-BMIPP (dynamic study). Early and delayed myocardial single photon emission computed tomography (SPECT) images were expressed as Bull's eyes and the myocardium was divided into four segments to calculate the washout rate for each segment on early and late SPECT images (early and late SPECT study). No significant differences in autonomic nervous function were observed between the two groups in heart rate variability. In a dynamic study, the reduction rate from the time activity curve was significantly higher in the IFN group compared with the H group (reduction rate, IFN group, 5.3 +/- 3.7% vs H group, 1.2 +/- 3.3%; P < 0.05). In the early and delayed myocardial SPECT study, the washout rate for the IFN group was significantly increased in all myocardial areas compared to that in the H group. However, the metabolic disorder of fatty acids caused by IFN was reversed on the second 123I-BMIPP myocardial scintigraphy examination several months after IFN therapy. These results indicate that metabolic disorders of fatty acids caused by IFN therapy can be detected before abnormalities are observed by Holter-ECG or echocardiography.

In vivo chemistry of iofetamine HCl iodine-123 (IMP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldwin, R.M.; Wu, J.L.

1988-01-01

Application of chemical methods for characterizing the in vivo behavior of iofetamine HCI /sup 123/I (IMP) has shed light on the metabolism of iofetamine in animals and humans. A successful technique consists of ethyl acetate extraction of the metabolites from tissue samples acidified with perchloric acid, separation of the mixture by high performance liquid chromatography, and quantitation of the radioactive components with a sensitive scintillation detector. Metabolism of iofetamine HCI /sup 123/I proceeds sequentially from the N-isopropyl group on the amphetamine side chain. The first step, dealkylation to the primary amine p-iodoamphetamine (PIA), occurs readily in the brain, lungs, andmore » liver; activity in the brain and lungs consists of only IMP and PIA even 24 hr after administration. The rate-limiting step appears to be deamination to give the transitory intermediate p-iodophenylacetone, which is rapidly degraded to p-iodobenzoic acid and conjugated with glycine in the liver to give the end product of metabolism, p-iodohippuric acid, which is excreted through the kidneys in the urine.« less

Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer's Disease Affected Brain.

PubMed

Okumura, Yuki; Maya, Yoshifumi; Onishi, Takako; Shoyama, Yoshinari; Izawa, Akihiro; Nakamura, Daisaku; Tanifuji, Shigeyuki; Tanaka, Akihiro; Arano, Yasushi; Matsumoto, Hiroki

2018-04-06

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2- a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC 50 ) of 14.7 ± 6.07-87.6 ± 39.8 nM. In vitro autoradiography indicated that 123 I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123 I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1 H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [ 123 I]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

"Parkinson-dementia" diseases: a comparison by double tracer SPECT studies.

PubMed

Rossi, Carlo; Volterrani, Duccio; Nicoletti, Valentina; Manca, Gianpiero; Frosini, Daniela; Kiferle, Lorenzo; Unti, Elisa; De Feo, Paola; Bonuccelli, Ubaldo; Ceravolo, Roberto

2009-12-01

We performed 123I-FP-CIT/SPECT and ECD/SPECT in 30 patients with Parkinson's disease with dementia (PDD) and 30 patients with dementia with Lewy bodies (DLB) to evaluate whether presynaptic nigro-striatal function and/or cerebral perfusional pattern is different in these diseases. The striatal uptake of DAT tracer was statistically significantly lower in PDD and DLB with respect to control data (p < 0.0005), however no significant difference was found between PDD and DLB. Patients with PDD and DLB showed a significant reduction of rCBF (p < 0.001) in parieto-occipital and frontal areas, with respect to controls, but the comparison between the two groups did not result in any significant difference by SPM analysis. Finally no correlation was found between any regional perfusional changes and nigro-striatal dysfunction. We conclude that neither studies with 123I-FP-CIT nor ECD/SPECT were able to discriminate between DLB and PDD in vivo.

Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects.

PubMed

Bremner, J D; Baldwin, R; Horti, A; Staib, L H; Ng, C K; Tan, P Z; Zea-Ponce, Y; Zoghbi, S; Seibyl, J P; Soufer, R; Charney, D S; Innis, R B

1999-08-31

Although positron emission tomography (PET) and single photon emission computed tomography (SPECT) are increasingly used for quantitation of neuroreceptor binding, almost no studies to date have involved a direct comparison of the two. One study found a high level of agreement between the two techniques, although there was a systematic 30% increase in measures of benzodiazepine receptor binding in SPECT compared with PET. The purpose of the current study was to directly compare quantitation of benzodiazepine receptor binding in the same human subjects using PET and SPECT with high specific activity [11C]iomazenil and [123I]iomazenil, respectively. All subjects were administered a single bolus of high specific activity iomazenil labeled with 11C or 123I followed by dynamic PET or SPECT imaging of the brain. Arterial blood samples were obtained for measurement of metabolite-corrected radioligand in plasma. Compartmental modeling was used to fit values for kinetic rate constants of transfer of radioligand between plasma and brain compartments. These values were used for calculation of binding potential (BP = Bmax/Kd) and product of BP and the fraction of free non-protein-bound parent compound (V3'). Mean values for V3' in PET and SPECT were as follows: temporal cortex 23+/-5 and 22+/-3 ml/g, frontal cortex23+/-6 and 22+/-3 ml/g, occipital cortex 28+/-3 and 31+/-5 ml/g, and striatum 4+/-4 and 7+/-4 ml/g. These preliminary findings indicate that PET and SPECT provide comparable results in quantitation of neuroreceptor binding in the human brain.

Scatter and cross-talk correction for one-day acquisition of 123I-BMIPP and 99mtc-tetrofosmin myocardial SPECT.

PubMed

Kaneta, Tomohiro; Kurihara, Hideyuki; Hakamatsuka, Takashi; Ito, Hiroshi; Maruoka, Shin; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo

2004-12-01

123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TET) are widely used for evaluation of myocardial fatty acid metabolism and perfusion, respectively. ECG-gated TET SPECT is also used for evaluation of myocardial wall motion. These tests are often performed on the same day to minimize both the time required and inconvenience to patients and medical staff. However, as 123I and 99mTc have similar emission energies (159 keV and 140 keV, respectively), it is necessary to consider not only scattered photons, but also primary photons of each radionuclide detected in the wrong window (cross-talk). In this study, we developed and evaluated the effectiveness of a new scatter and cross-talk correction imaging protocol. Fourteen patients with ischemic heart disease or heart failure (8 men and 6 women with a mean age of 69.4 yr, ranging from 45 to 94 yr) were enrolled in this study. In the routine one-day acquisition protocol, BMIPP SPECT was performed in the morning, with TET SPECT performed 4 h later. An additional SPECT was performed just before injection of TET with the energy window for 99mTc. These data correspond to the scatter and cross-talk factor of the next TET SPECT. The correction was performed by subtraction of the scatter and cross-talk factor from TET SPECT. Data are presented as means +/- S.E. Statistical analyses were performed using Wilcoxon's matched-pairs signed-ranks test, and p < 0.05 was considered significant. The percentage of scatter and cross-talk relative to the corrected total count was 26.0 +/- 5.3%. EDV and ESV after correction were significantly greater than those before correction (p = 0.019 and 0.016, respectively). After correction, EF was smaller than that before correction, but the difference was not significant. Perfusion scores (17 segments per heart) were significantly lower after as compared with those before correction (p < 0.001). Scatter and cross-talk correction revealed significant differences in EDV, ESV, and perfusion scores. These observations indicate that scatter and cross-talk correction is required for one-day acquisition of 123I-BMIPP and 99mTc-tetrofosmin SPECT.

European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis.

PubMed

Varrone, Andrea; Dickson, John C; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, Ozlem L; Kluge, Andreas; Knudsen, Gitte M; Koulibaly, Pierre Malick; Nobili, Flavio; Pagani, Marco; Sabri, Osama; Vander Borght, Thierry; Van Laere, Koen; Tatsch, Klaus

2013-01-01

Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls. SPECT data from 139 healthy controls (74 men, 65 women; age range 20-83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR). A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade. This study provides a large database of [(123)I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using [(123)I]FP-CIT SPECT as the imaging marker.

Cerebral blood flow and freezing of gait in Parkinson's disease.

PubMed

Imamura, K; Okayasu, N; Nagatsu, T

2012-09-01

We investigated the relationship between freezing of gait (FOG) severity in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) and evaluated the effect of selegiline therapy. We evaluated 54 patients with PD (FOG positive: 21 patients, and FOG negative: 33 patients) with N-isopropyl-p-[I-123] iodoamphetamine ((123) I-IMP) SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory. [Correction added on 18 April 2012, after online publication: In the preceding statement, 55 instead of 54 patients with PD were evaluated, and FOG negative consisted of 34 instead of 33 patients] Furthermore, we examined rCBF in FOG-negative patients treated with levodopa with or without selegiline. Z-values of bilateral Brodmann areas (BA) 10 and 11 and left BA32 showed significant increases in the FOG-positive group compared with the FOG-negative group. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] There were significantly positive correlations between Z-values of these areas and FOG score, especially on both sides of BA11. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] An increase in Z-values in bilateral BA10 and 11 and left BA32 in the levodopa-selegiline treatment group after 1 year was significantly inhibited compared with the levodopa treatment group. [Correction added on 18 April 2012, after online publication: In the preceding statement, left BA32 was changed to right BA32, and Z-values was changed to Z-scores] There was a close relationship between FOG severity in PD and an increase in rCBF in BA 10, 11 and 32. Furthermore, selegiline's FOG prevention effect may be related to maintaining rCBF in these same areas. © 2012 John Wiley & Sons A/S.

Combined thallium-201 and dynamic iodine-123 iodophenylpentadecanoic acid single-photon emission computed tomography in patients after acute myocardial infarction with effective reperfusion.

PubMed

Richter, W S; Beckmann, S; Cordes, M; Schuppenhauer, T; Schartl, M; Munz, D L

2000-12-01

Considerable derangements of energy metabolism are to be expected during ischemia and reperfusion. In ischemic myocardium, the oxidative degradation of carbohydrates is shifted toward the anaerobic production of lactate and the oxidation of fatty acids is suppressed. The aim of this study was to examine the uptake and metabolism of iodine-123 (123I) iodophenylpentadecanoic acid (IPPA) in stunned myocardium. In 15 patients, SPECT with 201Tl and 123I IPPA as well as echocardiography with low-dose dobutamine stimulation were performed 12 +/- 5 days after myocardial infarction with reperfusion. Follow-up echocardiography was carried out 24 +/- 8 days later for documentation of functional improvement. Uptake of 201Tl and 123I IPPA were obtained in five left ventricular segments, and dynamic SPECT imaging was used for calculation of the fast and the slow components of the biexponential myocardial 123I IPPA clearance. Wall motion improved in 14 of 26 dysfunctional segments (54%). Stunned segments were characterized by a reduced 123I IPPA extraction, a shorter half-life of the fast, and a longer half-life of the slow clearance component. All parameters of the combined 201Tl/123I IPPA study predicted functional recovery with similar accuracies (area under the receiver operator characteristic curves between 0.68 and 0.76; p = NS). Analysis of 201Tl uptake alone could not predict functional recovery in this study. Stunned myocardium is characterized by a disturbance of fatty acid metabolism. For prediction of functional improvement, 123I IPPA imaging added significant diagnostic information.

Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

PubMed

Langston, J William; Wiley, Jesse C; Tagliati, Michele

2018-01-01

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining 123 I-ioflupane SPECT and the noradrenergic receptor ligand 123 I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral 123 I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

Scatter and cross-talk corrections in simultaneous Tc-99m/I-123 brain SPECT using constrained factor analysis and artificial neural networks

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Maksud, P.; Kijewski, M. F.; Haberi, M. O.; Todd-Pokropek, A.; Aurengo, A.; Moore, S. C.

2000-08-01

Simultaneous imaging of Tc-99m and I-123 would have a high clinical potential in the assessment of brain perfusion (Tc-99m) and neurotransmission (I-123) but is hindered by cross-talk between the two radionuclides. Monte Carlo simulations of 15 different dual-isotope studies were performed using a digital brain phantom. Several physiologic Tc-99m and I-123 uptake patterns were modeled in the brain structures. Two methods were considered to correct for cross-talk from both scattered and unscattered photons: constrained spectral factor analysis (SFA) and artificial neural networks (ANN). The accuracy and precision of reconstructed pixel values within several brain structures were compared to those obtained with an energy windowing method (WSA). In I-123 images, mean bias was close to 10% in all structures for SFA and ANN and between 14% (in the caudate nucleus) and 25% (in the cerebellum) for WSA. Tc-99m activity was overestimated by 35% in the cortex and 53% in the caudate nucleus with WSA, but by less than 9% in all structures with SFA and ANN. SFA and ANN performed well even in the presence of high-energy I-123 photons. The accuracy was greatly improved by incorporating the contamination into the SFA model or in the learning phase for ANN. SFA and ANN are promising approaches to correct for cross-talk in simultaneous Tc-99m/I-123 SPECT.

Radiosynthesis and evaluation of novel acetylcholine receptor radioligands

NASA Astrophysics Data System (ADS)

Pimlott, Sally L.

Neuroreceptor single photon emission computed tomography (SPECT) imaging provides a powerful tool for the evaluation of the function of a neurotransmitter system in normal and or disease states in the living human brain. The cholinergic system is involved in the control of a variety of complex functions including learning, memory and modulation of behaviour. Deficits in the cholinergic system have been found in a number of neurological diseases, such as Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Epilepsy. Acetylcholine receptors (AChRs) are divided into two classes, muscarinic and nicotinic. The aim of this project was to develop two novel SPECT AChR ligands: (R,R)[123I]I-QNB, a M1 subtype selective muscarinic acetylcholine receptor (mAChR) ligand, and 5-[123I]-A-85380, a alpha4beta2 subtype selective nicotinic receptor (nAChR) ligand, for use in human SPECT imaging studies. The calculation of the binding potential of a ligand can be used to obtain quantitative information from a SPECT scan, enabling comparisons to be made between studies. Methodological issues involved in the calculation of binding potential are therefore crucial for the accuracy of results. A particularly important parameter is the amount of authentic radioligand available to cross the blood brain barrier. This was characterised in the research performed for this thesis. The radiosynthesis of two novel neuroreceptor radioligands has been optimised for use in humans. (R, R)[123I]I-QNB has been used in human studies to provide useful information on the human mAChR function in disease. Pre-clinical evaluation of 5-[123I]-A-85380 provided useful information for in vivo human studies. Both radioligands are concluded to successfully provide novel information on the function of the acetylcholine system. Methodological issues involved in the blood metabolite analysis and measurement of plasma protein binding have been investigated and discussed, with particular reference made to the factors that must be taken into account when designing these experiments. (Abstract shortened by ProQuest.).

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S; Endres, Christopher; Foss, Catherine

2013-01-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.

2013-06-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Design of a short nonuniform acquisition protocol for quantitative analysis in dynamic cardiac SPECT imaging - a retrospective 123 I-MIBG animal study.

PubMed

Zan, Yunlong; Long, Yong; Chen, Kewei; Li, Biao; Huang, Qiu; Gullberg, Grant T

2017-07-01

Our previous works have found that quantitative analysis of 123 I-MIBG kinetics in the rat heart with dynamic single-photon emission computed tomography (SPECT) offers the potential to quantify the innervation integrity at an early stage of left ventricular hypertrophy. However, conventional protocols involving a long acquisition time for dynamic imaging reduce the animal survival rate and thus make longitudinal analysis difficult. The goal of this work was to develop a procedure to reduce the total acquisition time by selecting nonuniform acquisition times for projection views while maintaining the accuracy and precision of estimated physiologic parameters. Taking dynamic cardiac imaging with 123 I-MIBG in rats as an example, we generated time activity curves (TACs) of regions of interest (ROIs) as ground truths based on a direct four-dimensional reconstruction of experimental data acquired from a rotating SPECT camera, where TACs represented as the coefficients of B-spline basis functions were used to estimate compartmental model parameters. By iteratively adjusting the knots (i.e., control points) of B-spline basis functions, new TACs were created according to two rules: accuracy and precision. The accuracy criterion allocates the knots to achieve low relative entropy between the estimated left ventricular blood pool TAC and its ground truth so that the estimated input function approximates its real value and thus the procedure yields an accurate estimate of model parameters. The precision criterion, via the D-optimal method, forces the estimated parameters to be as precise as possible, with minimum variances. Based on the final knots obtained, a new protocol of 30 min was built with a shorter acquisition time that maintained a 5% error in estimating rate constants of the compartment model. This was evaluated through digital simulations. The simulation results showed that our method was able to reduce the acquisition time from 100 to 30 min for the cardiac study of rats with 123 I-MIBG. Compared to a uniform interval dynamic SPECT protocol (1 s acquisition interval, 30 min acquisition time), the newly proposed protocol with nonuniform interval achieved comparable (K1 and k2, P = 0.5745 for K1 and P = 0.0604 for k2) or better (Distribution Volume, DV, P = 0.0004) performance for parameter estimates with less storage and shorter computational time. In this study, a procedure was devised to shorten the acquisition time while maintaining the accuracy and precision of estimated physiologic parameters in dynamic SPECT imaging. The procedure was designed for 123 I-MIBG cardiac imaging in rat studies; however, it has the potential to be extended to other applications, including patient studies involving the acquisition of dynamic SPECT data. © 2017 American Association of Physicists in Medicine.

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

PubMed

Ko, Toshiyuki; Utanohara, Yuko; Suzuki, Yasuhiro; Kurihara, Makiko; Iguchi, Nobuo; Umemura, Jun; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

2016-01-01

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.

Automated MicroSPECT/MicroCT Image Analysis of the Mouse Thyroid Gland.

PubMed

Cheng, Peng; Hollingsworth, Brynn; Scarberry, Daniel; Shen, Daniel H; Powell, Kimerly; Smart, Sean C; Beech, John; Sheng, Xiaochao; Kirschner, Lawrence S; Menq, Chia-Hsiang; Jhiang, Sissy M

2017-11-01

The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve 131 I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer. A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post injection of 123 I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively. FVB/N mice with normal thyroid glands and TgBRAF V600E mice with thyroid tumors were imaged. In-house CTViewer software was developed to streamline image analysis with new capabilities, along with display of 3D voxel-based 123 I gamma photon intensity in MATLAB. The customized mouse cradle facilitates consistent tissue configuration among image acquisitions such that rigid body registration can be applied to align serial images of the same mouse via the in-house CTViewer software. CTViewer is designed specifically to streamline SPECT/CT image analysis with functions tailored to quantify thyroid radioiodine uptake. Automatic segmentation of thyroid volumes of interest (VOI) from adjacent salivary glands in t1 images is enabled by superimposing the thyroid VOI from the t24 image onto the corresponding aligned t1 image. The extent of heterogeneity in 123 I accumulation within thyroid VOIs can be visualized by 3D display of voxel-based 123 I gamma photon intensity. MicroSPECT/CT image acquisition and analysis for thyroidal RAI uptake is greatly improved by the cradle and the CTViewer software, respectively. Furthermore, the approach of superimposing thyroid VOIs from t24 images to select thyroid VOIs on corresponding aligned t1 images can be applied to studies in which the target tissue has differential radiotracer retention from surrounding tissues.

Use of a polysulfone hemodialysis membrane may prevent recurrent posterior reversible encephalopathy syndrome in a patient undergoing hemodialysis.

PubMed

Mima, Akira; Matsubara, Takeshi; Endo, Shuichiro; Murakami, Taichi; Hashimoto, Yasuki

2014-01-01

A 71-year-old woman underwent hemodialysis (HD) treatment for chronic kidney disease. During HD, she developed headache, abnormalities in visual perception, and generalized convulsion. Brain magnetic resonance imaging (MRI) showed T2-hyperintensity lesions in the posterior lobe, and an electroencephalogram showed slow waves in all areas. Twenty days later, the T2-hyperintensity lesions had vanished. Furthermore, perfusion computed tomography (CT) and single-photon emission CT with N-isopropyl[(123)I]-p-iodoamphetamine (IMP-SPECT) showed no significant abnormalities. The patient was diagnosed with posterior reversible encephalopathy syndrome (PRES) because she displayed typical clinical symptoms and MRI findings. Although several antihypertensive and antiseizure medications were administered, the patient experienced recurrent PRES. Therefore, we used a polysulfone dialyzer to reduce the oxidative stress and inflammation while preserving vascular endothelial function. After use of a polysulfone dialyzer membrane, the patient had no PRES episodes during the clinical course. This is the first study to demonstrate that use of a polysulfone dialyzer membrane instead of a cellulose membrane may prevent recurrent PRES.

Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma.

PubMed

Liu, Xiang; Pham, Tien Q; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc'h, Christian; Katsifis, Andrew

2008-10-01

A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. [(123)I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. The iodonicotinamides displayed low-affinity binding for sigma(1)-sigma(2) receptors (K(i)>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[(123)I]iodonicotinamide ([(123)I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ( approximately 8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [(123)I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [(123)I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [(123)I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. These findings suggest that [(123)I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

Endocrine radionuclide scintigraphy with fusion single photon emission computed tomography/computed tomography

PubMed Central

Wong, Ka-Kit; Gandhi, Arpit; Viglianti, Benjamin L; Fig, Lorraine M; Rubello, Domenico; Gross, Milton D

2016-01-01

AIM: To review the benefits of single photon emission computed tomography (SPECT)/computed tomography (CT) hybrid imaging for diagnosis of various endocrine disorders. METHODS: We performed MEDLINE and PubMed searches using the terms: “SPECT/CT”; “functional anatomic mapping”; “transmission emission tomography”; “parathyroid adenoma”; “thyroid cancer”; “neuroendocrine tumor”; “adrenal”; “pheochromocytoma”; “paraganglioma”; in order to identify relevant articles published in English during the years 2003 to 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (case reports, reviews, meta-analyses and abstracts) concerning the application of SPECT/CT to endocrine imaging were analyzed to provide a descriptive synthesis of the utility of this technology. RESULTS: The emergence of hybrid SPECT/CT camera technology now allows simultaneous acquisition of combined multi-modality imaging, with seamless fusion of three-dimensional volume datasets. The usefulness of combining functional information to depict the bio-distribution of radiotracers that map cellular processes of the endocrine system and tumors of endocrine origin, with anatomy derived from CT, has improved the diagnostic capability of scintigraphy for a range of disorders of endocrine gland function. The literature describes benefits of SPECT/CT for 99mTc-sestamibi parathyroid scintigraphy and 99mTc-pertechnetate thyroid scintigraphy, 123I- or 131I-radioiodine for staging of differentiated thyroid carcinoma, 111In- and 99mTc- labeled somatostatin receptor analogues for detection of neuroendocrine tumors, 131I-norcholesterol (NP-59) scans for assessment of adrenal cortical hyperfunction, and 123I- or 131I-metaiodobenzylguanidine imaging for evaluation of pheochromocytoma and paraganglioma. CONCLUSION: SPECT/CT exploits the synergism between the functional information from radiopharmaceutical imaging and anatomy from CT, translating to improved diagnostic accuracy and meaningful impact on patient care. PMID:27358692

Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study

PubMed Central

Stoffers, D.; Winogrodzka, A.; Isaias, I.-U.; Costantino, G.; Pezzoli, G.; Ferrarese, C.; Antonini, A.; Wolters, E.-Ch.; Booij, J.

2008-01-01

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson’s disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [123I]β-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PDT) and without tremor (PDWT) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [123I]β-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PDT than in the PDWT subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [123I]β-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset. PMID:18335163

Cerebral blood-flow tomography: xenon-133 compared with isopropyl-amphetamine-iodine-123: concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lassen, N.A.; Henriksen, L.; Holm, S.

1983-01-01

Tomographic maps of local cerebral blood flow (CBF) were obtained with xenon-133 and with isopropyl-amphetamine-iodine-123 (IMP) in 11 subjects: one normal, two tumor cases, and eight cerebrovascular cases. A highly sensitive four-face, rapidly rotating, single-photon emission tomograph was used. The Xe-133 flow maps are essentially based on the average Xe-133 concentration over the initial 2 min during and after an inhalation of the inert gas lasting 1 min. These maps agreed very well with the early IMP maps obtained over the initial 10 min following an i.v. bolus injection. The subsequent IMP tomograms showed a slight decrease in contrast amountingmore » to appr. five percentage points in the CBF ratio between diseased and contralateral areas. It is concluded that Xe-133 is more practical: low cost, available on a 7-day basis, easily repeatable, quantifiable without the need for arterial sampling, and with low radiation exposure to patient and personnel. On the other hand, IMP gives an image of slightly higher resolution. It also introduces a new class of iodinated brain-seeking compounds allowing, perhaps, imaging of other functions more important than mere blood flow.« less

[A Phase 1 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP)].

PubMed

Torizuka, K; Yonekura, Y; Nishimura, T; Tamaki, N; Uehara, T; Ikekubo, K; Hino, M

1991-07-01

Phase 1 study of beta-methyl-p-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), a new radiopharmaceutical developed for the evaluation of myocardial fatty acid metabolism, was performed in six normal volunteers to evaluate its biodistribution and safety. After intravenous injection of 111 MBq of 123I-BMIPP, the agent accumulated to the myocardium rapidly (5.4 +/- 0.6% at 1.5 hr after injection) and was washed-out slowly (5.1 +/- 0.4% at 3.0hr). 123I-BMIPP demonstrated no significant accumulation to any specific organs other than myocardium, liver and muscle. Myocardium was clearly visualized in the planar and SPECT images obtained 30 min and 3 hrs after injection. The absorption doses from 123I-BMIPP estimated by MIRD method were lower than those from 201Tl in all organs. Neither adverse reactions nor abnormal clinical laboratory findings were found in the safety evaluation. These results suggest 123I-BMIPP is a promising agent for evaluating myocardial fatty acid metabolism.

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury.

PubMed

Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

2017-12-01

Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients. The subjects of this study were seven patients who suffered from neurobehavioral disability. They underwent IMZ SPECT and FMZ PET. Nondisplaceable binding potential (BP ND ) was calculated from FMZ PET images. The uptake of IMZ was evaluated on the basis of lesion-to-pons ratio (LPR). The locations of low uptake levels were visually evaluated both in IMZ SPECT and FMZ PET images. We compared FMZ BP ND and (LPR-1) of IMZ SPECT. In the visual assessment, FMZ BP ND decreased in 11 regions. In IMZ SPECT, low uptake levels were observed in eight of the 11 regions. The rate of concordance between FMZ PET and IMZ SPECT was 72.7%. The mean values IMZ (LPR-1) (1.95 ± 1.01) was significantly lower than that of FMZ BP ND (2.95 ± 0.80 mL/mL). There was good correlation between FMZ BP ND and IMZ (LPR-1) (r = 0.80). IMZ SPECT findings were almost the same as FMZ PET findings in TBI patients. The results indicated that IMZ SPECT is useful for evaluating the loss of neuronal integrity. Because IMZ SPECT can be performed in various facilities, IMZ SPECT may become widely adopted for evaluating the loss of neuronal integrity.

Iofetamine hydrochloride I 123: a new radiopharmaceutical for cerebral perfusion imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Druckenbrod, R.W.; Williams, C.C.; Gelfand, M.J.

1989-01-01

Iofetamine hydrochloride I-123 permits cerebral blood perfusion imaging with single photon emission computed tomography (SPECT). SPECT is more widely available than positron emission tomography, and complements anatomic visualization with X-ray computed tomography (CT) or magnetic resonance imaging. Iofetamine is an amphetamine analog that is rapidly taken up by the lungs, then redistributed principally to the liver and brain. The precise mechanism of localization has not been determined, but is believed to result from nonspecific receptor binding. Brain uptake peaks at 30 minutes postinjection and remains relatively constant through 60 minutes. The drug is metabolized and excreted in the urine, withmore » negligible activity remaining at 48 hours. When compared with CT in stroke patients, visualization may be performed sooner after symptom onset and a larger zone of involvement may be evident with iofetamine. Localization of seizure foci and diagnosis of Alzheimer's disease may also be possible. As CT has revolutionized noninvasive imaging of brain anatomy, SPECT with iofetamine permits routine cerebral blood flow imaging. 36 references.« less

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

DOE PAGES

Reutter, Bryan W.; Huesman, Ronald H.; Brennan, Kathleen M.; ...

2011-01-01

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123 I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness ofmore » this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123 I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.« less

Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell

2015-05-01

Malignant melanoma expresses a highly aggressive metastasis. Early diagnosis of malignant melanoma is important for patient survival. Radiolabeled benzamides and nicotinamides have been reported to be attractive candidates for malignant melanoma diagnosis as they bind to melanin, a characteristic substance that displays in malignant melanoma, and show high tumor accumulation and retention. Herein, we designed and synthesized a novel (123/131)I-labeled nicotinamide derivative that specifically binds to melanin. (123/131)I-Iochlonicotinamide was prepared with good radiochemical yield (50-70%, decay corrected) and high specific radioactivity (50-80 GBq/μmol). (131)I-Iochlonicotinamide exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. High uptake of (123/131)I-Iochlonicotinamide in B16F0 melanoma cells compared to that in A375 amelanotic cells demonstrated its selective binding to melanin. Intravenous administration of (123/131)I-Iochlonicotinamide in a melanoma-bearing mouse model revealed high uptake in melanotic melanoma and high tumor-to-muscle ratio. MicroSPECT scan of (123/131)I-Iochlonicotinamide injected mice also displayed high contrast tumor imaging as compared with normal organs. The radiation-absorbed dose projection for the administration of (131)I-Iochlonicotinamide to human was based on the results of biodistribution study. The effective dose appears to be approximately 0.44 mSv/MBq(-1). The specific binding of (123/131)I-Iochlonicotinamide to melanin along with a prolonged tumor retention and acceptable projected human dosimetry suggest that it may be a promising theranostic agent for treating malignant melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study.

PubMed

Hedon, Christophe; Huet, Fabien; Ben Bouallegue, Fayçal; Vernhet, Hélène; Macia, Jean-Christophe; Cung, Thien-Tri; Leclercq, Florence; Cade, Stéphane; Cransac, Frédéric; Lattuca, Benoit; Vandenberghe, D'Arcy; Bourdon, Aurélie; Benkiran, Meriem; Vauchot, Fabien; Gervasoni, Richard; D'estanque, Emmanuel; Mariano-Goulart, Denis; Roubille, François

2018-02-01

Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Generalized five-dimensional dynamic and spectral factor analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Fakhri, Georges; Sitek, Arkadiusz; Zimmerman, Robert E.

2006-04-15

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming thatmore » primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where {sup 99m}Tc and {sup 123}I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary {sup 99m}Tc (bias=6.4%{+-}4.3%) and {sup 123}I (-1.7%{+-}6.9%) time activity curves (TAC) compared to conventional FADS (biases=15.5%{+-}10.6% in {sup 99m}Tc and 8.3%{+-}12.7% in {sup 123}I, p<0.05). Our technique was also validated in two primate dynamic dual isotope perfusion/DAT transporter studies. Biases of {sup 99m}Tc-HMPAO and {sup 123}I-DAT activity estimates with respect to estimates obtained in the presence of only one radionuclide (sequential imaging) were significantly lower with 5D-GFA (9.4%{+-}4.3% for {sup 99m}Tc-HMPAO and 8.7%{+-}4.1% for {sup 123}I-DAT) compared to biases greater than 15% for volumes of interest (VOI) over the reconstructed volumes (p<0.05). 5D-GFA is a novel and promising approach in dynamic SPECT imaging that can also be used in other modalities. It allows accurate and precise dynamic analysis while compensating for Compton scatter and cross-talk.« less

Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ueda, Masashi; Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501; Fukushima, Takahiro

Highlights: • We developed a radioiodinated peptide probe targeting αvβ6 integrin ({sup 123}I-IFMDV2). • {sup 123}I-IFMDV2 had a high affinity and selectivity for αvβ6 integrin. • {sup 123}I-IFMDV2 showed a specific binding to αvβ6 integrin in vivo. • {sup 123}I-IFMDV2 enabled clear visualization of the αvβ6-integrin-positive tumor. - Abstract: Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-related death. Since significant upregulation of αvβ6 integrin has been reported in PDAC, this integrin is a promising target for PDAC detection. In this study, we aimed to develop a radioiodinated probe for the imaging of αvβ6 integrin-positive PDAC with single-photonmore » emission computed tomography (SPECT). Methods: Four peptide probes were synthesized and screened by competitive and saturation binding assays using 2 PDAC cell lines (AsPC-1, αvβ6 integrin-positive; MIA PaCa-2, αvβ6 integrin-negative). The probe showing the best affinity was used to study the biodistribution assay, an in vivo blocking study, and SPECT imaging using tumor bearing mice. Autoradiography and immunohistochemical analysis were also performed. Results: Among the 4 probes examined in this study, {sup 125}I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of {sup 125}I-IFMDV2 in the AsPC-1 xenograft was 3–5 times greater than that in the MIA PaCa-2 xenograft, consistent with the expression of αvβ6 integrin in each xenograft, and confirmed by immunohistochemistry. Pretreatment with excess amounts of A20FMDV2 significantly blocked the accumulation of {sup 125}I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, {sup 123}I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: {sup 123}I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC.« less

Myocardial Uptake of 7′-(Z)-[123I]Iodorotenone During Vasodilator Stress in Dogs With Critical Coronary Stenoses

PubMed Central

Broisat, Alexis; Ruiz, Mirta; Goodman, Norman C.; Hanrahan, Stephen M.; Reutter, Bryan W.; Brennan, Kathleen M.; Janabi, Mustafa; Schaefer, Saul; Watson, Denny D.; Beller, George A.; VanBrocklin, Henry F.; Glover, David K.

2013-01-01

Background There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[125I]iodorotenone (125I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of 123I-ZIROT in an intact large-animal model. Methods and Results The 123I-ZIROT was administered during adenosine A2A agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, 123I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. 123I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At 123I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial 123I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or 99mTc-sestamibi from previous studies using a similar model. Furthermore, the 123I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). Conclusions The ability of 123I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment. PMID:21917783

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease.

PubMed

Colloby, Sean J; O'Brien, John T; Fenwick, John D; Firbank, Michael J; Burn, David J; McKeith, Ian G; Williams, E David

2004-11-01

Dopaminergic loss can be visualised using (123)I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of (123)I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer's disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject's image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P

123I-Mibg scintigraphy and 18F-Fdg-Pet imaging for diagnosing neuroblastoma

PubMed Central

Bleeker, Gitta; Tytgat, Godelieve Am; Adam, Judit A; Caron, Huib N; Kremer, Leontien Cm; Hooft, Lotty; van Dalen, Elvira C

2015-01-01

Background Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood. Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (123I-MIBG), which can be used for imaging the tumour. Moreover, 123I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of 123I-MIBG scintigraphy to detect neuroblastoma varies according to the literature. Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of 123I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of 123I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. Objectives Primary objectives: 1.1 To determine the diagnostic accuracy of 123I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 1.2 To determine the diagnostic accuracy of negative 123I-MIBG scintigraphy in combination with 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. Secondary objectives: 2.1 To determine the diagnostic accuracy of 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 2.2 To compare the diagnostic accuracy of 123I-MIBG (SPECT-CT) and 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. This was performed within and between included studies. 123I-MIBG (SPECT-CT) scintigraphy was the comparator test in this case. Search methods We searched the databases of MEDLINE/PubMed (1945 to 11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially relevant articles. Also we checked the reference lists of relevant articles and review articles, scanned conference proceedings and searched for unpublished studies by contacting researchers involved in this area. Selection criteria We included studies of a cross-sectional design or cases series of proven neuroblastoma, either retrospective or prospective, if they compared the results of 123I-MIBG (SPECT-CT) scintigraphy or 18F-FDG-PET(-CT) imaging, or both, with the reference standards or with each other. Studies had to be primary diagnostic and report on children aged between 0 to 18 years old with a neuroblastoma of any stage at first diagnosis or at recurrence. Data collection and analysis One review author performed the initial screening of identified references. Two review authors independently performed the study selection, extracted data and assessed the methodological quality. We used data from two-by-two tables, describing at least the number of patients with a true positive test and the number of patients with a false negative test, to calculate the sensitivity, and if possible, the specificity for each included study. If possible, we generated forest plots showing estimates of sensitivity and specificity together with 95% confidence intervals. Main results Eleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of 123I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of 123I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies. One study reported on the diagnostic accuracy of 18F-FDG-PET(-CT) imaging (add-on test) in patients with negative 123I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative 123I-MIBG scan and a positive 18F-FDG-PET(-CT) scan. The sensitivity of 18F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to 123I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of 18F-FDG-PET(-CT) imaging was 100% versus 92% of 123I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities. Authors' conclusions The reported sensitivities of 123-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma. Only one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made. As described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate 123I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be 18F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed. The diagnostic accuracy of 18F-FDG-PET(-CT) imaging in case of a negative 123I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test 123I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search. At the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term "the sensitivity to assess the presence of neuroblastoma" instead of "diagnostic accuracy" for the objectives. PLAIN LANGUAGE SUMMARY 123I-MIBG- and 18F-FDG-PET-imaging, two nuclear imaging methods for diagnosing neuroblastoma tumours Background and rationale Neuroblastoma is a childhood tumour that can be visualized by a specific nuclear imaging compound, called metaiodobenzylguanidine (123I -MIBG). 123I-MIBG-imaging is not only important for the diagnosis of neuroblastoma, but also for localization of metastases (spread of the disease to other organs). Sometimes, the neuroblastoma does not take up 123I-MIBG and as a result the neuroblastoma is not visible on the scan. In that case, another type of nuclear imaging might be useful to visualize the neuroblastoma: fluoro-deoxy-glucose – positron emission tomography (18F-FDG-PET)-imaging. In the literature the ability to discriminate between neuroblastoma and non-neuroblastoma lesions for these two types of nuclear imaging methods vary. Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on scoring the amount of metastases per body segment visible on 123I-MIBG scans. Therefore, it is important to determine the exact ability to discriminate between neuroblastoma and non-neuroblastoma on 123I-MIBG-imaging and 18F-FDG-PET-imaging. We reviewed the evidence about the accuracy of 123I-MIBG-imaging and 18F-FDG-PET-imaging for the detection of a neuroblastoma in children suspected of this disease. Study characteristics We searched scientific databases for clinical studies comparing 123I-MIBG or 18F-FDG-PET imaging, or both, with microscopic examination of tissue suspected of neuroblastoma (histopathology). The evidence is current up to 11 September 2012. We identified 11 eligible studies including 621 children that fulfilled our inclusion criteria: children < 18 years old with a neuroblastoma and 123I-MIBG or 18F-FDG-PET imaging or both. All studies included proven neuroblastoma. Quality of the evidence All 11 included studies had methodological limitations. Only one included study provided data on specificity (the ability of a test to correctly classify an individual as 'disease-free') and therefore we could not perform all of the planned analyses. Key results When compared to histopathological results the sensitivity (the ability of a test to correctly classify an individual person as 'diseased') of 123I-MIBG imaging varied from 67% to 100% in patients with histologically proven neuroblastoma. This means that in 100 children with proven neuroblastoma 123I-MIBG imaging will correctly identify 67 to 100 of the neuroblastoma cases. Only one study, that reported on a lesion level, provided data to calculate the specificity (the ability of a test to correctly classify an individual as 'disease-free'): 68% in 115 lesions. This means that of 100 disease-free lesions in patients with proven neuroblastoma 123I-MIBG imaging will correctly identify 68 lesions. So, in about 10% of the cases the neuroblastoma is not visible on 123I-MIBG imaging (false negative results). For these cases, it is advisable to perform an additional test like 18F-FDG-PET imaging, but to be certain of its clinical value, more evidence is needed. Only one included study reported on false positive findings. This means that 123I-MIBG imaging and 18F-FDG-PET imaging incorrectly identified neuroblastoma lesions in patients which might result in wrongly classifying a patient with metastatic disease. It is important to keep in mind that false positive findings can occur, although more research is needed before definitive conclusions can be made. We could not determine the diagnostic accuracy of 18F-FDG-PET imaging, in case the neuroblastoma was incorrectly not identified with 123I-MIBG, due to limited data. Also, we could not calculate the diagnostic accuracy of 18F-FDG-PET imaging for detecting a neuroblastoma and compare this to 123I-MIBG imaging because of the limited available data. PMID:26417712

Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study.

PubMed

McKeith, Ian; O'Brien, John; Walker, Zuzana; Tatsch, Klaus; Booij, Jan; Darcourt, Jacques; Padovani, Alessandro; Giubbini, Raffaele; Bonuccelli, Ubaldo; Volterrani, Duccio; Holmes, Clive; Kemp, Paul; Tabet, Naji; Meyer, Ines; Reininger, Cornelia

2007-04-01

Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025. Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events. A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.

Atomoxetine administration combined with intensive speech therapy for post-stroke aphasia: evaluation by a novel SPECT method.

PubMed

Yamada, Naoki; Kakuda, Wataru; Yamamoto, Kazuma; Momosaki, Ryo; Abo, Masahiro

2016-09-01

We clarified the safety, feasibility, and efficacy of atomoxetine administration combined with intensive speech therapy (ST) for patients with post-stroke aphasia. In addition, we investigated the effect of atomoxetine treatment on neural activity of surrounding lesioned brain areas. Four adult patients with motor-dominant aphasia and a history of left hemispheric stroke were studied. We have registered on the clinical trials database (ID: JMA-IIA00215). Daily atomoxetine administration of 40 mg was initiated two weeks before admission and raised to 80 mg 1 week before admission. During the subsequent 13-day hospitalization, administration of atomoxetine was raised to 120 mg and daily intensive ST (120 min/day, one-on-one training) was provided. Language function was assessed using the Japanese version of The Western Aphasia Battery (WAB) and the Token test two weeks prior to admission, on the day of admission, and at discharge. At two weeks prior to admission and at discharge, each patient's cortical blood flow was measured using (123)I-IMP-single photon emission computed tomography (SPECT). This protocol was successfully completed by all patients without any adverse effects. Four patients showed improved language function with the median of the Token Test increasing from 141 to 149, and the repetition score of WAB increasing from 88 to 99. In addition, cortical blood flow surrounding lesioned brain areas was found to increase following intervention in all patients. Atomoxetine administration and intensive ST were safe and feasible for post-stroke aphasia, suggesting their potential usefulness in the treatment of this patient population.

Pathophysiologic study of chronic infarcts with I-123 isopropyl iodo-amphetamine (IMP): the importance of periinfarct area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raynaud, C.; Rancurel, G.; Samson, Y.

1987-01-01

Seventeen chronic cerebral infarcts were investigated by a highly sensitive, dedicated brain single photon emission computerized tomography system using /sup 123/I-isopropyl iodoamphetamine (IMP) and /sup 133/Xe. IMP uptake was measured 10 minutes, 2 hours, and 5 hours after injection, and regional cerebral blood flow was measured with 133Xe. In 4 cases a positron emission tomography system was used to measure the rCBF and the regional metabolic rate of oxygen with C15O2 and 15O2. The results obtained allowed us to identify 2 abnormal zones. One, the central area, was characterized by a severe decrease in IMP uptake and rCBF averaging 34%more » and 46% respectively and by a hypodense image on the x-ray computerized tomography scan. The second, the periinfarct or ''peripheral area'' was characterized by a moderate decrease in IMP uptake and regional cerebral blood flow averaging 13 and 19% respectively; this area extended around the central area and had a normal density on computerized tomography scan. The IMP hypofixation of the peripheral area observed at the 10th minute tended to disappear at the 5th hour. The volume of this area was often found to be quite large, covering more than 30% of a hemisphere whereas the central area did not exceed 25%. Volume appeared to be correlated with the neurological status of the patient. The nature of the peripheral area is not established with certainty. It may be caused by deafferentation of areas not directly affected by the ischemic insult and/or selective ischemic neuronal loss. The results stress the important role played by the peripheral area, which may be useful in establishing the prognosis and evaluating the efficacy of therapy in individual stroke cases.« less

Absolute activity quantitation from projections using an analytical approach: comparison with iterative methods in Tc-99m and I-123 brain SPECT

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Kijewski, M. F.; Moore, S. C.

2001-06-01

Estimates of SPECT activity within certain deep brain structures could be useful for clinical tasks such as early prediction of Alzheimer's disease with Tc-99m or Parkinson's disease with I-123; however, such estimates are biased by poor spatial resolution and inaccurate scatter and attenuation corrections. We compared an analytical approach (AA) of more accurate quantitation to a slower iterative approach (IA). Monte Carlo simulated projections of 12 normal and 12 pathologic Tc-99m perfusion studies, as well as 12, normal and 12 pathologic I-123 neurotransmission studies, were generated using a digital brain phantom and corrected for scatter by a multispectral fitting procedure. The AA included attenuation correction by a modified Metz-Fan algorithm and activity estimation by a technique that incorporated Metz filtering to compensate for variable collimator response (VCR), IA-modeled attenuation, and VCR in the projector/backprojector of an ordered subsets-expectation maximization (OSEM) algorithm. Bias and standard deviation over the 12 normal and 12 pathologic patients were calculated with respect to the reference values in the corpus callosum, caudate nucleus, and putamen. The IA and AA yielded similar quantitation results in both Tc-99m and I-123 studies in all brain structures considered in both normal and pathologic patients. The bias with respect to the reference activity distributions was less than 7% for Tc-99m studies, but greater than 30% for I-123 studies, due to partial volume effect in the striata. Our results were validated using I-123 physical acquisitions of an anthropomorphic brain phantom. The IA yielded quantitation accuracy comparable to that obtained with IA, while requiring much less processing time. However, in most conditions, IA yielded lower noise for the same bias than did AA.

[Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency].

PubMed

Watanabe, K; Miyajima, S; Kusano, Y; Tanabe, N; Hirokawa, Y

1997-07-01

A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.

5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.

PubMed

Waelbers, Tim; Polis, Ingeborgh; Vermeire, Simon; Dobbeleir, André; Eersels, Jos; De Spiegeleer, Bart; Audenaert, Kurt; Slegers, Guido; Peremans, Kathelijne

2013-08-01

Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046). This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and (123)I-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.

Myocardial viability assessment with dynamic low-dose iodine-123-iodophenylpentadecanoic acid metabolic imaging: comparison with myocardial biopsy and reinjection SPECT thallium after myocardial infarction.

PubMed

Murray, G L; Schad, N C; Magill, H L; Vander Zwaag, R

1994-04-01

Aggressive cardiac revascularization requires recognition of stunned and hibernating myocardium, and cost considerations may well govern the technique used. Dynamic low-dose (1 mCi) [123I]iodophenylpentadecanoic acid (IPPA) metabolic imaging is a potential alternative to PET using either 18FDG or 15O-water. Resting IPPA images were obtained from patients with severe ischemic cardiomyopathy, and transmural myocardial biopsies were obtained during coronary bypass surgery to confirm viability. Thirty-nine of 43 (91%) biopsies confirmed the results of the IPPA images with a sensitivity for viability of 33/36 (92%) and a specificity of 6/7 (86%). Postoperatively, wall motion improved in 80% of IPPA-viable, dysfunctional segments. Furthermore, when compared to reinjection thallium (SPECT-TI) scans after myocardial infarction, IPPA-SPECT-TI concordance occurred in 27/35 (77%) (K = 0.536, p = 0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-TI, 26/35 (74%) versus 18/35 (51%) (p = 0.047). Metabolic IPPA cardiac viability imaging is a safe, inexpensive technique that may be a useful alternative to PET.

Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, M.B.; Lake, R.R.; Graham, L.S.

1989-10-01

Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n ({sup 123}I)IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake inmore » the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. Hypofrontality was not observed.« less

Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study.

PubMed

Iranzo, Alex; Valldeoriola, Francesc; Lomeña, Francisco; Molinuevo, José Luis; Serradell, Mónica; Salamero, Manel; Cot, Albert; Ros, Domènec; Pavía, Javier; Santamaria, Joan; Tolosa, Eduardo

2011-09-01

Serial dopamine transporter (DAT) imaging in patients with Parkinson's disease (PD) and other synucleinopathies shows progressive nigrostriatal dopaminergic dysfunction. Because idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can precede the classic symptoms of PD and other synucleinopathies, we postulated that serial DAT imaging in patients with IRBD could be used to detect decline in striatal tracer uptake, indicating progressive nigrostriatal cell degeneration. In a prospective study, 20 patients with IRBD (mean age 70·55 years [SD 6·02]) underwent serial DAT imaging with (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-FP-CIT) SPECT at baseline and again after 1·5 years and 3 years; 20 age-matched and sex-matched control participants (69·50 years [6·77]) underwent imaging at baseline and 3 years. The striatum to occipital cortex uptake ratios were calculated for the putamen and caudate nucleus in each hemisphere. In patients, the ratio was judged to be reduced when it was less than two SD of the mean ratio in controls at the same timepoint. Differences in (123)I-FP-CIT uptake between patients and controls in each striatal region and rates of decline were assessed by use of multivariate ANOVA (MANOVA). Compared with controls, patients had significantly reduced mean (123)I-FP-CIT binding in all four striatal regions at baseline and after 3 years. Striatal (123)I-FP-CIT uptake was reduced compared with that in controls in ten patients at baseline and in 13 patients after 3 years. In patients, the mean reduction in (123)I-FP-CIT uptake from baseline to 3 years was 19·36% (95% CI 15·14 to 23·59) in the left putamen, 15·57% (10·87 to 20·28) in the right putamen, 10·81% (6·49 to 15·18) in the left caudate nucleus, and 7·14% (2·74 to 11·56) in the right caudate nucleus. After adjustment for the baseline (123)I-FP-CIT uptake ratios, the decline in (123)I-FP-CIT binding at baseline to 3 years was significantly greater in patients than in controls in the left putamen (9·78% difference between groups, 95% CI 3·22 to 16·32), right putamen (5·43%, 1·99 to 12·86), and left caudate nucleus (8·07%, 1·44 to 14·70), but not in the right caudate nucleus (4·16%, -3·00 to 11·34). At the 3-year assessment, three patients were diagnosed with PD. These patients had the lowest (123)I-FP-CIT uptake at baseline and a mean reduction in (123)I-FP-CIT uptake at 3 years of 32·81% in the left putamen, 30·40% in the right putamen, 26·51% in the left caudate nucleus, and 23·75% in the right caudate nucleus. In patients with IRBD, serial (123)I-FP-CIT SPECT shows decline in striatal tracer uptake that reflects progressive nigrostriatal dopaminergic dysfunction. Serial (123)I-FP-CIT SPECT can be used to monitor the progression of nigrostriatal deficits in patients with IRBD, and could be useful in studies of potential disease-modifying compounds in these patients. Fondo de Investigaciones Sanitarias of Spain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study.

PubMed

Menéndez-González, Manuel; Tavares, Francisco; Zeidan, Nahla; Salas-Pacheco, José M; Arias-Carrión, Oscar

2014-01-01

The [(123)I]ioflupane-a dopamine transporter radioligand-SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X-associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinson's disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Clinical usefulness of dopamine transporter SPECT imaging with 123I-FP-CIT in patients with possible dementia with Lewy bodies: randomised study.

PubMed

Walker, Zuzana; Moreno, Emilio; Thomas, Alan; Inglis, Fraser; Tabet, Naji; Rainer, Michael; Pizzolato, Gilberto; Padovani, Alessandro

2015-02-01

Dementia with Lewy bodies (DLB) is underrecognised in clinical settings. To investigate whether performing a (123)I-ioflupane injection ((123)I-FP-CIT also called DaTSCAN™) single photon emission computed tomography (SPECT) scan in patients with possible DLB would lead to a more certain diagnosis (probable DLB or non-DLB dementia). We randomised 187 patients with possible DLB 2:1 to have a scan or not (control group). The outcome measure was a change in diagnosis to probable DLB or non-DLB. There were 56 controls and 114 scanned patients, of whom 43% had an abnormal scan. More patients in the imaging group had a change in diagnosis compared with controls at 8 and 24 weeks (61% (n = 70) v. 4% (n = 2) and 71% (n = 77) v. 16% (n = 9); both P<0.0001). Clinicians were more likely to change the diagnosis if the scan was abnormal (82%) than if it was normal (46%). Imaging significantly contributed to a more certain diagnosis, proving to be a useful adjunct in the work-up of patients with possible DLB. Royal College of Psychiatrists.

Cerebral perfusion imaging in Alzheimer's disease. Use of single photon emission computed tomography and iofetamine hydrochloride I 123

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, K.A.; Mueller, S.T.; Walshe, T.M.

1987-02-01

We used single photon emission computed tomography (SPECT) to study 15 patients with Alzheimer's disease and nine controls. Iofetamine hydrochloride I 123 uptake data were recorded from the entire brain using a rotating gamma camera. Activity ratios were measured for the frontal, posterior parietal, posterior, medial, and lateral cortical temporal regions and striate cortex and were normalized by the activity in the cerebellum. Abnormalities in iofetamine hydrochloride I 123 activity were similar to the abnormalities in glucose metabolism observed with positron emission tomography. Cortical tracer activity was globally depressed in patients with Alzheimer's disease, with the greatest reduction in themore » posterior parietal cortex.« less

Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study.

PubMed

Klein, Nikolas; Sacher, Julia; Geiss-Granadia, Thomas; Mossaheb, Nilufar; Attarbaschi, Trawat; Lanzenberger, Rupert; Spindelegger, Christoph; Holik, Alexander; Asenbaum, Susanne; Dudczak, Robert; Tauscher, Johannes; Kasper, Siegfried

2007-04-01

Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT). Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [(123)I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake. At 6 h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for escitalopram and 64.0 +/- 12.7% for citalopram (p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/- 11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain. The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.

Ischaemic memory imaging using metabolic radiopharmaceuticals: overview of clinical settings and ongoing investigations.

PubMed

Yoshinaga, Keiichiro; Naya, Masanao; Shiga, Tohru; Suzuki, Eriko; Tamaki, Nagara

2014-02-01

"Ischaemic memory" is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). β-Methyl-p-[(123)I]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of (123)I-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with (18)F-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations.

Molecular imaging of angiogenesis with SPECT

PubMed Central

Boerman, Otto C.

2010-01-01

Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: 99mTc (Emax 141 keV, T1/2 6.02 h), 123I (Emax 529 keV, T1/2 13.0 h) and 111In (Emax 245 keV, T1/2 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed. PMID:20617435

A case of variant biochemical phenotype of Niemann-Pick disease type C accompanying savant syndrome.

PubMed

Hamatani, Mio; Jingami, Naoto; Uemura, Kengo; Nakasone, Naoe; Kinoshita, Hisanori; Yamakado, Hodaka; Ninomiya, Haruaki; Takahashi, Ryosuke

2016-06-22

A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis of schizophrenia in his teenage. He also developed a savant skill of calendar calculating. (123)I-IMP-SPECT showed decreased cerebral blood flow in the left frontotemporal lobe as often seen in savant syndrome. Although genetic analysis of NPC1 and NPC2 revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance.

Dynamic molecular imaging of cardiac innervation using a dual headpinhole SPECT system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Jicun; Boutchko, Rostyslav; Sitek, Arkadiusz

2008-03-29

Typically 123I-MIBG is used for the study of innervation andfunction of the sympathetic nervous system in heart failure. The protocolinvolves two studies: first a planar or SPECT scan is performed tomeasure initial uptake of the tracer, followed some 3-4 hours later byanother study measuring the wash-out of the tracer from the heart. A fastwash-out is indicative of a compromised heart. In this work, a dual headpinhole SPECT system was used for imaging the distribution and kineticsof 123I-MIBG in the myocardium of spontaneous hypertensive rats (SHR) andnormotensive Wistar Kyoto (WKY) rats. The system geometry was calibratedbased on a nonlinear point projectionmore » fitting method using a three-pointsource phantom. The angle variation effect of the parameters was modeledwith a sinusoidal function. A dynamic acquisition was performed byinjecting 123I-MIBG into rats immediately after starting the dataacquisition. The detectors rotated continuously performing a 360o dataacquisition every 90 seconds. We applied the factor analysis (FA)methodand region of interest (ROI) sampling method to obtain time activitycurves (TACs)in the blood pool and myocardium and then appliedtwo-compartment modeling to estimate the kinetic parameters. Since theinitial injection bolus is too fast for obtaining a consistenttomographic data set in the first few minutes of the study, we appliedthe FA method directly to projections during the first rotation. Then thetime active curves for blood and myocardial tissue were obtained from ROIsampling. The method was applied to determine if there were differencesin the kinetics between SHR and WKY rats and requires less time byreplacing the delayed scan at 3-4 hours after injection with a dynamicacquisition over 90 to 120 minutes. The results of a faster washout and asmaller distribution volume of 123IMIBG near the end of life in the SHRmodel of hypertrophic cardiomyopthy may be indicative of a failing heartin late stages of heart failure.« less

Sex differences in availability of β2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers

PubMed Central

Cosgrove, Kelly P.; Esterlis, Irina; McKee, Sherry A.; Bois, Frederic; Seibyl, John P.; Mazure, Carolyn M.; Krishnan-Sarin, Suchitra; Staley, Julie K.; Picciotto, Marina R.; O’Malley, Stephanie S.

2012-01-01

Context Sex differences exist in the reinforcing effects of nicotine, smoking cessation rates, and in response to nicotine replacement therapies. Sex differences in availability of nicotinic acetylcholine receptors containing the β2 subunit (β2*-nAChRs) may underlie differential nicotine and tobacco smoking effects and related behaviors in women and men. Objective To examine β2*-nAChR availability between male and female smokers and nonsmokers. To determine relationships between β2*-nAChR availability and tobacco smoking characteristics and female sex steroid hormones. Design Male (n=26) and female (n=28) tobacco smokers participated in one [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT) scan at 7–9 days of abstinence. Age-matched male (n=26) and female (n=30) nonsmokers participated in a single [123I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Setting Academic Imaging Center Participants Tobacco smokers (n=54) and age- and sex-matched nonsmokers (n=56). Main Outcome Measure [123I]5-IA SPECT images were converted to equilibrium distribution volumes and analyzed using regions-of-interest. Results β2*-nAChR availability was significantly higher in male smokers compared to male nonsmokers in striatum, cortex and cerebellum, but female smokers did not have higher β2*-nAChR availability than female nonsmokers in any region. In women, β2*-nAChR availability in the cortex and cerebellum was negatively and significantly correlated with progesterone level on the day of the scan. In female smokers, on the day of the scan, progesterone levels were positively and significantly correlated with depressive symptoms, craving for a cigarette, and nicotine withdrawal. Conclusions The regulatory effects of nicotine in the brain, i.e., tobacco-smoking induced upregulation of β2*-nAChRs, appear to be distinctly different between men and women, and female sex hormones likely play a role in this regulation. These findings suggest an underlying neurochemical mechanism for the reported behavioral sex differences. In order to treat female smokers more effectively, it is critical that non-nicotinic mediated medications are explored. PMID:22474108

Preparation and biologic evaluation of a novel radioiodinated benzylpiperazine, 123I-MEL037, for malignant melanoma.

PubMed

Pham, Tien Q; Berghofer, Paula; Liu, Xiang; Greguric, Ivan; Dikic, Branko; Ballantyne, Patrice; Mattner, Filomena; Nguyen, Vu; Loc'h, Christian; Katsifis, Andrew

2007-08-01

Radiopharmaceuticals that can target the random metastatic dissemination of melanoma tumors may present opportunities for imaging and staging the disease as well as potential radiotherapeutic applications. A novel molecule, 2-(2-(4-(4-(123)I-iodobenzyl)piperazin-1-yl)-2-oxoethyl)isoindoline-1,3-dione (MEL037), was synthesized, labeled with 123I, and evaluated for application in melanoma tumor scintigraphy and radiotherapy. The tumor imaging potential of 123I-MEL037 was studied in vivo in C57BL/6J female mice bearing the B16F0 murine melanoma tumor and in BALB/c nude mice bearing the A375 human amelanotic melanoma tumor by biodistribution, competition studies, and SPECT. 123I-MEL037 exhibited high and rapid uptake in the B16F0 melanoma tumor at 1 h (13 %ID/g [percentage injected dose per gram]), increasing with time to reach 25 %ID/g at 6 h. A significant uptake was also observed in the eyes (2 %ID, at 3-6 h after injection) of black mice. No uptake was observed in the tumor or in the eyes of nude mice bearing the A375 tumor. Because of high uptake and long retention in the tumor and rapid body clearance, the mean contrast ratios (MCR) of 123I-MEL037 were 30 and 60, at 24 and 48 h after injection, respectively. At 24 h after injection of mice bearing the B16 melanoma, SPECT indicated that the radioactivity was located predominately in the tumor followed by the eyes, whereas no specific localization of the radioactivity was noted in mice bearing the A375 human amelanotic tumor. In competition experiments, uptake of 123I-MEL037 in brain, lung, heart, and kidney--organs known to contain sigma-receptors--was not significantly different in haloperidol-treated animals compared with control animals. Therefore, reduction of uptake in tumor and eyes of the pigmented mice bearing the B16F0 tumor suggested that the mechanism of tumor uptake was likely due to an interaction with melanin. These findings suggested that 123I-MEL037, which displays a rapid and very high tumor uptake, appeared to be a promising imaging agent for detection of most melanoma tumors with the potential for development as a therapeutic agent in melanoma tumor proliferation.

Influence of education on cognitive performance and dopamine transporter binding in dementia with Lewy bodies.

PubMed

Lamotte, Guillaume; Morello, Rémy; Lebasnier, Adrien; Agostini, Denis; Bouvard, Gérard; De La Sayette, Vincent; Defer, Gilles L

2016-07-01

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common forms of dementia. These two diseases share some clinical and pathological similarities, yet the loss of dopaminergic neurons confirmed by 123-I-Ioflupane Single Photon Emission Computed Tomography (SPECT) is a suggestive feature of DLB. Current evidence suggests that higher education has a protective effect on the risk of developing clinical AD. However, how education influences cognitive performance and the presynaptic dopamine transporter marker in DLB is unknown. We reviewed 56 consecutive patients with DLB who underwent a 123-I-Ioflupane SPECT from January 2009 to August 2013 at the University Hospital of Caen. We collected clinical and neuropsychological data from medical files and 123-I-Ioflupane SPECT data for all patients. There was no correlation between education and global cognitive performance in patients with DLB. However, there was a positive correlation between education and tests exploring visuoconstructive functions (Rey complex figure copy and recall) and verbal retrieval strategies (Grober and Buschke free recall test). There was also a positive correlation between education and dopamine transporter binding. Higher educated patients had higher binding in the striatum, putamen and caudate nucleus (p=0.001 for each regions of interest). Dopamine transporter binding in the striatum, putamen and caudate nucleus was lower in the subgroup of patients with REM sleep behavior disorder, but was not associated with other DLB symptoms. Higher education may have a protective effect on visuoconstructive performance and verbal retrieval strategies and may influence dopaminergic nigrostriatal neurodegeneration in patients with DLB. Copyright © 2016 Elsevier B.V. All rights reserved.

No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT.

PubMed

Thomsen, Gerda; Knudsen, Gitte Moos; Jensen, Peter S; Ziebell, Morten; Holst, Klaus K; Asenbaum, Susanne; Booij, Jan; Darcourt, Jacques; Dickson, John C; Kapucu, Ozlem L; Nobili, Flavio; Sabri, Osama; Sera, Terez; Tatsch, Klaus; Tossici-Bolt, Livia; Laere, Koen Van; Borght, Thierry Vander; Varrone, Andrea; Pagani, Marco; Pinborg, Lars Hageman

2013-05-20

Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10 different European countries. The striatal measure of DAT availability was analyzed in a multiple regression model with age, SPECT centre and smoking as predictor. There was no statistically significant difference in DAT availability between the groups of active smokers, ex-smokers and non-smokers (p = 0.34). Further, we could not demonstrate a significant association between striatal DAT and the number of cigarettes per day or total lifetime cigarette packages in smokers and ex-smokers. Our results do not support the hypothesis that large differences in striatal DAT availability are present in smokers compared to ex-smokers and healthy volunteers with no history of smoking.

Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia.

PubMed

Shi, Cindy Q; Young, Lawrence H; Daher, Edouard; DiBella, Edward V R; Liu, Yi-Hwa; Heller, Eliot N; Zoghbi, Sami; Wackers, Frans J Th; Soufer, Robert; Sinusas, Albert J

2002-03-01

Myocardial ischemia is associated with reduced free fatty acid (FFA) beta-oxidation and increased glucose utilization. This study evaluated the potential of dynamic SPECT imaging of a FFA analog, p-(123)I-iodophenylpentadecanoic acid (IPPA), for detection of ischemia and compares retention of IPPA with (18)F-FDG accumulation. In a canine model of regional low-flow ischemia (n = 9), serial IPPA SPECT images (2 min per image) were acquired over 52--90 min. In a subset of dogs (n = 6), (18)F-FDG was injected after completing SPECT imaging and allowed to accumulate for 40 min before killing the animals. Flow was assessed with radiolabeled microspheres. Myocardial metabolism was evaluated independently by selective coronary arterial and venous sampling. Serial IPPA SPECT images showed an initial defect in the ischemic region (0.70% plus minus 0.03% ischemic-to-nonischemic ratio), which normalized within 48 min because of the slower IPPA clearance from the ischemic region (t(1/2) = 54.2 plus minus 3.3 min) relative to the nonischemic region (t(1/2) = 36.7 plus minus 5.6 min) (P < 0.05). Delayed myocardial IPPA and (18)F-FDG activities were correlated (r = 0.70; n = 576 segments), and both were maximally increased in segments with a moderate flow reduction (IPPA, 151% of nonischemic; (18)F-FDG, 450% of nonischemic; P < 0.05). Serial SPECT imaging showed delayed myocardial clearance of IPPA in ischemic regions with moderate flow reduction, which lead to increased late myocardial retention of IPPA. Retention of IPPA correlated with (18)F-FDG accumulation, supporting the potential of IPPA as a noninvasive marker of ischemic myocardium.

Differences in serotonin transporter binding affinity in patients with major depressive disorder and night eating syndrome.

PubMed

Lundgren, J D; Amsterdam, J; Newberg, A; Allison, K C; Wintering, N; Stunkard, A J

2009-03-01

We examined serotonin transporter (SERT) binding affinity using single photon emission computed tomography (SPECT) in patients with major depressive disorder (MDD) and night eating syndrome (NES). There are similarities between MDD and NES in affective symptoms, appetite disturbance, nighttime awakenings, and, particularly, response to selective serotonin reuptake inhibitors (SSRIs). Six non-depressed patients with NES and seven patients with MDD underwent SPECT brain imaging with 123I-ADAM, a radiopharmaceutical agent selective for SERT sites. Uptake ratios of 123I-ADAM SERT binding were obtained for the midbrain, basal ganglia, and temporal lobe regions compared to the cerebellum reference region. Patients with NES had significantly greater SERT uptake ratios (effect size range 0.64-0.84) in the midbrain, right temporal lobe, and left temporal lobe regions than those with MDD whom we had previously studied. Pathophysiological differences in SERT uptake between patients with NES and MDD suggest these are distinct clinical syndromes.

[Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane].

PubMed

García-Gómez, F J; García-Solís, D; Luis-Simón, F J; Marín-Oyaga, V A; Carrillo, F; Mir, P; Vázquez-Albertino, R J

2013-01-01

Statistical parametric mapping (SPM) is a widely used produced for normalization of functional images. This study has aimed to develop a normalization template of (123)I-Ioflupane SPECT-imaging DaTSCAN(®), GE Healthcare), not available in SPM5, and to validate it compared to other quantification methods. In order to write the template we retrospectively selected 26 subjects who had no evidence of nigrostriatal degeneration and whose age distribution was similar to that of the patients in the usual practice of our Department: 2 subjects (7.6%) were < 35 years, 9 between 35-65 years (34.6%) and 15 > 65 years (57.7%). All the studies were normalized with the T1-template available in SPM5 and an average image of the value was obtained for each voxel. For validation we analyzed 60 patients: 30 with idiopathic Parkinson's disease patients (iPD) with right involvement (66.83±12.20 years) and 30 with essential tremor patients (ET) (67.27±8.33 years). Specific uptake rates (SUR) of different striatal regions were compared after image normalization with our template and the application of a semiautomated VOIs-map created with Analyze v9.0 ((©)BIR, Mayo Clinic), against two quantification methods: a) manual adjustment of a ROIs-map drawn in Analyze, and b) semi-automated method (HERMES-BRASS) with normalization and implementation of VOIs-map. No statistically significant differences in the iPD/ET discriminatory capacity between the three methods analyzed were observed (p<0,001). The correlation of SUR after normalization with our «template» was higher than that obtained by method b) (R>0,871, p<0,001). This difference was greater in patients with PD. Our study demonstrates the efficacy of our SPM «template» for (123)I-Ioflupane SPECT-imaging, obtained from normalization with «T1-template». Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Thyroid Carcinoma

PubMed

Ahmed, Najeeb; Niyaz, Kashif; Borakati, Aditya; Marafi, Fahad; Birk, Rubinder; Usmani, Sharjeel

2018-02-26

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice. Creative Commons Attribution License

Receiver-operating-characteristic analysis of an automated program for analyzing striatal uptake of 123I-ioflupane SPECT images: calibration using visual reads.

PubMed

Kuo, Phillip Hsin; Avery, Ryan; Krupinski, Elizabeth; Lei, Hong; Bauer, Adam; Sherman, Scott; McMillan, Natalie; Seibyl, John; Zubal, George

2013-03-01

A fully automated objective striatal analysis (OSA) program that quantitates dopamine transporter uptake in subjects with suspected Parkinson's disease was applied to images from clinical (123)I-ioflupane studies. The striatal binding ratios or alternatively the specific binding ratio (SBR) of the lowest putamen uptake was computed, and receiver-operating-characteristic (ROC) analysis was applied to 94 subjects to determine the best discriminator using this quantitative method. Ninety-four (123)I-ioflupane SPECT scans were analyzed from patients referred to our clinical imaging department and were reconstructed using the manufacturer-supplied reconstruction and filtering parameters for the radiotracer. Three trained readers conducted independent visual interpretations and reported each case as either normal or showing dopaminergic deficit (abnormal). The same images were analyzed using the OSA software, which locates the striatal and occipital structures and places regions of interest on the caudate and putamen. Additionally, the OSA places a region of interest on the occipital region that is used to calculate the background-subtracted SBR. The lower SBR of the 2 putamen regions was taken as the quantitative report. The 33 normal (bilateral comma-shaped striata) and 61 abnormal (unilateral or bilateral dopaminergic deficit) studies were analyzed to generate ROC curves. Twenty-nine of the scans were interpreted as normal and 59 as abnormal by all 3 readers. For 12 scans, the 3 readers did not unanimously agree in their interpretations (discordant). The ROC analysis, which used the visual-majority-consensus interpretation from the readers as the gold standard, yielded an area under the curve of 0.958 when using 1.08 as the threshold SBR for the lowest putamen. The sensitivity and specificity of the automated quantitative analysis were 95% and 89%, respectively. The OSA program delivers SBR quantitative values that have a high sensitivity and specificity, compared with visual interpretations by trained nuclear medicine readers. Such a program could be a helpful aid for readers not yet experienced with (123)I-ioflupane SPECT images and if further adapted and validated may be useful to assess disease progression during pharmaceutical testing of therapies.

Usefulness of the convexity apparent hyperperfusion sign in 123I-iodoamphetamine brain perfusion SPECT for the diagnosis of idiopathic normal pressure hydrocephalus.

PubMed

Ohmichi, Takuma; Kondo, Masaki; Itsukage, Masahiro; Koizumi, Hidetaka; Matsushima, Shigenori; Kuriyama, Nagato; Ishii, Kazunari; Mori, Etsuro; Yamada, Kei; Mizuno, Toshiki; Tokuda, Takahiko

2018-03-16

OBJECTIVE The gold standard for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is the CSF removal test. For elderly patients, however, a less invasive diagnostic method is required. On MRI, high-convexity tightness was reported to be an important finding for the diagnosis of iNPH. On SPECT, patients with iNPH often show hyperperfusion of the high-convexity area. The authors tested 2 hypotheses regarding the SPECT finding: 1) it is relative hyperperfusion reflecting the increased gray matter density of the convexity, and 2) it is useful for the diagnosis of iNPH. The authors termed the SPECT finding the convexity apparent hyperperfusion (CAPPAH) sign. METHODS Two clinical studies were conducted. In study 1, SPECT was performed for 20 patients suspected of having iNPH, and regional cerebral blood flow (rCBF) of the high-convexity area was examined using quantitative analysis. Clinical differences between patients with the CAPPAH sign (CAP) and those without it (NCAP) were also compared. In study 2, the CAPPAH sign was retrospectively assessed in 30 patients with iNPH and 19 healthy controls using SPECT images and 3D stereotactic surface projection. RESULTS In study 1, rCBF of the high-convexity area of the CAP group was calculated as 35.2-43.7 ml/min/100 g, which is not higher than normal values of rCBF determined by SPECT. The NCAP group showed lower cognitive function and weaker responses to the removal of CSF than the CAP group. In study 2, the CAPPAH sign was positive only in patients with iNPH (24/30) and not in controls (sensitivity 80%, specificity 100%). The coincidence rate between tight high convexity on MRI and the CAPPAH sign was very high (28/30). CONCLUSIONS Patients with iNPH showed hyperperfusion of the high-convexity area on SPECT; however, the presence of the CAPPAH sign did not indicate real hyperperfusion of rCBF in the high-convexity area. The authors speculated that patients with iNPH without the CAPPAH sign, despite showing tight high convexity on MRI, might have comorbidities such as Alzheimer's disease.

Crossed Cerebellar Tracer Uptake on Acute-Stage 123I-Iomazenil SPECT Imaging Predicts 3-Month Functional Outcome in Patients With Nonfatal Hypertensive Putaminal or Thalamic Hemorrhage.

PubMed

Kojima, Daigo; Komoribayashi, Nobukazu; Omama, Shinichi; Oikawa, Kohki; Fujiwara, Shunrou; Kobayashi, Masakazu; Kubo, Yoshitaka; Terasaki, Kazunori; Ogasawara, Kuniaki

2018-06-01

Whereas SPECT images obtained 180 minutes after administration of I-iomazenil (IMZ) (late images) are proportional to the distribution of central benzodiazepine receptor-binding potential, SPECT images obtained within 30 minutes after I-IMZ administration (early images) correlate with regional brain perfusion. The aim of the present study was to determine whether crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage. Forty-six patients underwent early and late SPECT imaging with I-IMZ within 7 days after the onset of hemorrhage. A region of interest was automatically placed in the bilateral cerebellar hemispheres using a 3-dimensional stereotaxic region-of-interest template, and the ratio of the value in the cerebellar hemisphere contralateral to the affected side to that in the ipsilateral cerebellar hemisphere (ARcbl) was calculated in each patient. Each patient's physical function was measured using the modified Rankin scale (mRS) score 3 months after onset. The ARcbl on early (ρ = -0.511, P = 0.0003) and late (ρ = -0.714, P < 0.0001) images correlated with the mRS 3 months after the onset of hemorrhage. Multivariate analysis showed that only a low ARcbl in late images was significantly associated with a poor functional outcome (mRS score ≥3 at 3 months after onset) (95% confidence interval, 0.001-0.003; P = 0.0212). Crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage.

Localization of brain tumors with Indium-111 labeled somatostatin analogue and iodine-123-methyl tyrosine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroiss, A.; Boeck, F.; Auinger, C.

1994-05-01

The aim of this study was to compare the visualization of brain tumors with Iodine-123-Methyl Tyrosine (l-123-MT) and Indium-111-Octreotide (ln-111-Oc). We used l-123-MT (FZ-Seibersdorf), administering 222 MBq and planar images were performed 10min and 1hr after application. In 5 pts SPECT images were performed too. Not earlier than 48hrs 244 MBq In-111-Oc (OctreoScan{sup {reg_sign}}, Mallincrodt) were injected and planar images 4 and 24 hrs after application performed. In 9 pts SPECT images were performed (4hrs p.appl.). A digital Anger camera was used for data acquisition and processing (APEX 409A, Elscint). A total of 12 pts (8 male, 4 female agemore » ranging from 45-71 yrs) were investigated. using a region of interest technique tumor-to-brain tissue rations (T/BT) were calculated. Diagnosis of tumor was established by neurosurgical procedures. 6 pts with glioblastoma showed a high uptake with in-111-Oc (T/BT 1.7 {plus_minus}0.5) and also with l-123-MT T/BT: 1.5{plus_minus}0.4 (10 {prime}) and 1.45 {plus_minus}0.45 (1h). In 2 menigiomas the images with ln-111-Oc were very good (T/BT: 3.1, 3.6 (4hr pl)) and were negative with l-123-MT. In 4 metastases we found a low uptake in 2 pts with l-123-MT T/BT (10{prime}): 1.3 and 1.25; T/BT (1h): 1.25 and 1.2 and ln-111-Oc (T/BT (4h pl): 1.6 and 1.4). These were pts with brain metastases of adeno carcinoma. In two pts with brain metastases of small cell lung cancer we found good images with both substances I-123-MT T/BT: 1.6 and 1.7 (1h) and ln-111-Oc T/BT: 2.5 and 2.6 (4h pl). In summary, glioblastoma showed concordant images with both substances and also metastases, meningiomas showed discordant images. SPECT acquisition is possible with both substances and sometimes advisable.« less

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: comparison with rest-redistribution thallium 201 imaging.

PubMed

Iskandrian, A S; Powers, J; Cave, V; Wasserleben, V; Cassell, D; Heo, J

1995-01-01

This study examined the ability of dynamic 123I-labeled iodophenylpentadecanoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease. Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi 123I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34% +/- 11%). The segmental uptake was compared with that of rest-redistribution 201Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11 +/- 5 vs 10 +/- 5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (kappa = 0.78 +/- 0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (kappa = 0.54 +/- 0.04). However, there were more reversible IPPA defects than reversible thallium defects (7 +/- 4 vs 3 +/- 4 segments/patient; p = 0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33% +/- 11% to 39% +/- 12% (p = 0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10 +/- 4 vs 5 +/- 4 segments/patient; p = 0.075). 123I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment

PubMed Central

Burlison, Jared S.; Hartshorne, Michael F.; Voda, Alan M.; Cocks, Franklin H.

2013-01-01

Purpose We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). Materials and methods We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 123I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Results Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1–16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of 131I from Argenco HP 77. Conclusion SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals. PMID:24128897

Synthesis and characterization of a novel radioiodinated phenylacetamide and its homolog as theranostic agents for malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell

2016-01-01

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. This study reports the preparation and biological characterizations of N-(2-(diethylamino)ethyl)-2-(3-(123/131)I-iodo-4- hydroxyphenyl)acetamide and N-(2-(diethylamino)ethyl)-3-(3-(123/131)I-iodo-4-hydroxyphenyl)propanamide (123/131)I-IHPA and 123/131I-IHPP) as novel melanin-specific theranostic agents. These two tracers were hydrophilic, exhibited good serum stability and high binding affinity to melanin. In vitro and in vivo studies revealed rapid, high and tenacious uptakes of both 131I-IHPA and 131I-IHPP in melanotic B16F0 cell line and in C57BL/6 mice bearing B16F0 melanoma, but not in amelanonic A375 cell line and tumors. Small-animal SPECT imaging also clearly delineate B16F0 melanoma since 1 h postinjection of 123I-IHPA and 123I-IHPP in tumor-bearing mice. Owing to the favorable biodistribution of 131I-IHPA and 131I-IHPP after intravenous administration, the estimated absorption dose was low in most normal organs and relatively high in melanotic tumor. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and acceptable projected human dosimetry supported that these two tracers are promising theranostic agents for melanin-positive melanoma.

Recurrent malignant pheochromocytoma with unusual omental metastasis: 68Ga-DOTANOC PET/CT and 131I-MIBG SPECT/CT scintigraphy findings

PubMed Central

Arora, Saurabh; Agarwal, Krishan Kant; Karunanithi, Sellam; Tripathi, Madhavi; Kumar, Rakesh

2014-01-01

Pheochromocytomas are rare catecholamine-secreting tumors derived from the sympathetic nervous system. The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography (CT) or magnetic resonance imaging as well as functional imaging (e.g. with 123I/131I-MIBG (131I-metaiodobenzylguanidine) and 68Ga-DOTANOC (68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide) positron emission tomography (PET)/CT) to determine the extent and location of disease. We present a case of recurrent malignant pheochromocytoma with unusual site of metastasis in omentum, which was positive on 68Ga-DOTANOC PET/CT and 131I-MIBG single-photon emission computed tomography (SPECT/)/CT scintigraphy. PMID:25400380

Recurrent malignant pheochromocytoma with unusual omental metastasis: (68)Ga-DOTANOC PET/CT and (131)I-MIBG SPECT/CT scintigraphy findings.

PubMed

Arora, Saurabh; Agarwal, Krishan Kant; Karunanithi, Sellam; Tripathi, Madhavi; Kumar, Rakesh

2014-10-01

Pheochromocytomas are rare catecholamine-secreting tumors derived from the sympathetic nervous system. The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography (CT) or magnetic resonance imaging as well as functional imaging (e.g. with (123)I/(131)I-MIBG ((131)I-metaiodobenzylguanidine) and (68)Ga-DOTANOC ((68)Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide) positron emission tomography (PET)/CT) to determine the extent and location of disease. We present a case of recurrent malignant pheochromocytoma with unusual site of metastasis in omentum, which was positive on (68)Ga-DOTANOC PET/CT and (131)I-MIBG single-photon emission computed tomography (SPECT/)/CT scintigraphy.

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

PubMed Central

Nguyen Van, Tai; Hospital, Audrey; Lionne, Corinne; Jordheim, Lars P; Dumontet, Charles; Périgaud, Christian; Chaloin, Laurent

2016-01-01

Summary A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. PMID:27559400

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

PubMed

Klein, N; Sacher, J; Geiss-Granadia, T; Attarbaschi, T; Mossaheb, N; Lanzenberger, R; Pötzi, C; Holik, A; Spindelegger, C; Asenbaum, S; Dudczak, R; Tauscher, J; Kasper, S

2006-10-01

Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

Cortical damage following traumatic brain injury evaluated by iomazenil SPECT and in vivo microdialysis.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2013-01-01

[(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT) has been reported to be a useful marker of neuronal integrity. We evaluated cortical damage following traumatic brain injury (TBI) with IMZ SPECT at the acute stage. After conventional therapy for a cranial trauma, an IMZ SPECT re-evaluation was performed at the chronic stage. A reduction in IMZ uptake in the location of cerebral contusions was observed during the TBI acute phase; however, images of IMZ SPECT obtained during the chronic phase showed that areas with decreased IMZ distribution were remarkably reduced compared with those obtained during the acute phase. As a result of in vivo microdialysis study, the extracellular levels of glutamate in the cortex, where decreased IMZ distribution was shown during the acute phase, were increased during the 168-h monitoring period. During the chronic phase, IMZ uptake in the region with the microdialysis probes was recovered. The results suggest that this reduction in IMZ uptake might not be a sign of irreversible tissue damage in TBI.

Three modality image registration of brain SPECT/CT and MR images for quantitative analysis of dopamine transporter imaging

NASA Astrophysics Data System (ADS)

Yamaguchi, Yuzuho; Takeda, Yuta; Hara, Takeshi; Zhou, Xiangrong; Matsusako, Masaki; Tanaka, Yuki; Hosoya, Kazuhiko; Nihei, Tsutomu; Katafuchi, Tetsuro; Fujita, Hiroshi

2016-03-01

Important features in Parkinson's disease (PD) are degenerations and losses of dopamine neurons in corpus striatum. 123I-FP-CIT can visualize activities of the dopamine neurons. The activity radio of background to corpus striatum is used for diagnosis of PD and Dementia with Lewy Bodies (DLB). The specific activity can be observed in the corpus striatum on SPECT images, but the location and the shape of the corpus striatum on SPECT images only are often lost because of the low uptake. In contrast, MR images can visualize the locations of the corpus striatum. The purpose of this study was to realize a quantitative image analysis for the SPECT images by using image registration technique with brain MR images that can determine the region of corpus striatum. In this study, the image fusion technique was used to fuse SPECT and MR images by intervening CT image taken by SPECT/CT. The mutual information (MI) for image registration between CT and MR images was used for the registration. Six SPECT/CT and four MR scans of phantom materials are taken by changing the direction. As the results of the image registrations, 16 of 24 combinations were registered within 1.3mm. By applying the approach to 32 clinical SPECT/CT and MR cases, all of the cases were registered within 0.86mm. In conclusions, our registration method has a potential in superimposing MR images on SPECT images.

Imaging changes in synaptic acetylcholine availability in living human subjects

PubMed Central

Esterlis, Irina; Hannestad, Jonas O.; Bois, Frederic; Sewell, R. Andrew; Tyndale, Rachel; Seibyl, John P.; Picciotto, Marina R.; Laruelle, Marc; Carson, Richard E.; Cosgrove, Kelly P.

2013-01-01

Introduction In vivo estimation of beta2-nicotinic acetylcholine receptor (β2*-nAChR) availability with molecular neuroimaging is complicated by competition between the endogenous neurotransmitter ACh and the radioligand [123I]5-IA-85380 ([123I]5-IA). We examined whether binding of [123I]5-IA is sensitive to increases in extracellular levels of ACh in humans, as suggested in non-human primates (1). Methods Six healthy subjects (31±4yrs) participated in one [123I]5-IA SPECT study. After baseline scans, physostigmine (1–1.5mg) was administered IV over 60 min, and additional scans were collected (8–14h). Results We observed a significant reduction in VT/fp (total volume of distribution) after physostigmine (29±17% cortex, 19±15% thalamus, 19±15% striatum, and 36±30% cerebellum; p<.05). This reflected a combination of a region-specific 7–16% decrease in tissue concentration of tracer and 9% increase in plasma parent concentration. Conclusion These data suggest that increases in ACh compete with [123I]5-IA for binding to β2*-nAChRs. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular ACh. PMID:23160789

Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB.

PubMed

Thomas, Alan J; Attems, Johannes; Colloby, Sean J; O'Brien, John T; McKeith, Ian; Walker, Rodney; Lee, Lean; Burn, David; Lett, Debra J; Walker, Zuzana

2017-01-17

To conduct a validation study of 123 I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard. Patients >60 years of age with dementia who had undergone 123 I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123 I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria. Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123 I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123 I-FP-CIT imaging. This large autopsy analysis of 123 I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123 I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. This study provides Class I evidence that 123 I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB. Copyright © 2016 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

123/125I-labelled 2-iodo-L: -phenylalanine and 2-iodo-D: -phenylalanine: comparative uptake in various tumour types and biodistribution in mice.

PubMed

Kersemans, Veerle; Cornelissen, Bart; Kersemans, Ken; Bauwens, Matthias; Dierckx, Rudi A; De Spiegeleer, Bart; Mertens, John; Slegers, Guido

2006-08-01

In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models. Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al. Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed. In vitro testing demonstrated that [(123)I]-2-iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D: -isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [(123)I]-2-iodo-L: -phenylalanine. [(123)I]-2-iodo-L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics concerning radiation dose to other organs.

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina.

PubMed

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Mabuchi, Megumi; Naya, Masanao; Kawai, Yuko; Tamaki, Nagara

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123I-BMIPP single-photon emission computed tomography (SPECT) and 15O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with 123I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93+/-0.25, 0.86+/-0.21, 0.97+/-0.30, and 0.99+/-0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76+/-1.29, 1.84+/-0.74, 1.37+/-0.39, and 1.08+/-0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01+/-1.38, 2.20+/-0.95, 1.44+/-0.22, and 1.10+/-0.26, respectively. As 123I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced 123I-BMIPP uptake implies decreased MFR.

New horizons in cardiac innervation imaging: introduction of novel 18F-labeled PET tracers.

PubMed

Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A; Lapa, Constantin; Javadi, Mehrbod S; Higuchi, Takahiro

2017-12-01

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed.

In vivo evaluation and dosimetry of 123I-2-iodo-D-phenylalanine, a new potential tumor-specific tracer for SPECT, in an R1M rhabdomyosarcoma athymic mouse model.

PubMed

Kersemans, Veerle; Cornelissen, Bart; Bacher, Klaus; Kersemans, Ken; Thierens, Hubert; Dierckx, Rudi A; De Spiegeleer, Bart; Slegers, Guido; Mertens, John

2005-12-01

Earlier reports described the preferential uptake of d-amino acids in tumor-bearing mice. Moreover, it was shown that in tumor cells in vitro the L-amino acid transporter system seemed to lack stereospecificity. Because of the successful results with 123/125I-2-iodo-L-phenylalanine, 123/125I-2-iodo-D-phenylalanine was developed, and its tumor-detecting characteristics were evaluated in vivo. 123I labeling of 2-iodo-D-phenylalanine was performed with a kit formulation by use of Cu1+-assisted nucleophilic exchange. 123I-2-Iodo-D-phenylalanine was evaluated in R1M tumor-bearing athymic mice by dynamic planar imaging (DPI) and dissection. The in vivo stability of the tracer was tested by high-performance liquid chromatography. Tumor tracer retention and tracer contrast were evaluated as a function of time. Two-compartment blood modeling from DPI results and dosimetric calculations from biodistribution results were carried out. Moreover, 125I-2-iodo-D-phenylalanine and 18F-FDG uptake in acute inflammation was investigated. 123I-2-Iodo-D-phenylalanine was metabolically stable. Fast, high, and specific tumor retention was observed. Two-compartment modeling confirmed the fast clearance of the tracer through the kidneys to the bladder, as observed by DPI and dissection. Moreover, compared with the L-isomer, 123I-2-iodo-D-phenylalanine demonstrated faster clearance and faster uptake in the peripheral compartment. No accumulation in the abdomen or in the brain was noted. Dosimetry revealed that 123I-2-iodo-D-phenylalanine demonstrated a low radiation burden comparable to those of 123I-2-iodo-L-phenylalanine and 123I-2-iodo-L-tyrosine. Although 123I-2-iodo-D-phenylalanine showed a tumor retention of only 4%, the tumor contrast was increased up to 350% at 19 h after injection. 123I-2-Iodo-D-phenylalanine is a promising tracer for diagnostic oncologic imaging because of its high, fast, and specific tumor uptake and fast clearance from blood.

123I-BMIPP fatty acid analogue imaging is a novel diagnostic and prognostic approach following acute myocardial infarction.

PubMed

Biswas, S K; Sarai, M; Hishida, H; Ozaki, Y

2009-10-01

Fatty acid oxidation is the most efficient mode of myocardial energy production which requires a large amount of oxygen. Thus, alteration of fatty acid oxidation is considered to be a sensitive marker of ischaemia and myocardial damage. (123)I-BMIPP ([123]I-beta-methyl-p-iodophenylpentadecanoic acid) is a newly-investigated single-photon branching free fatty acid radiopharmaceutical with slow metabolism; thus, it is well-suited for single-photon emission computed tomography (SPECT). Assessment of fatty acid metabolism by radionuclide techniques has a potential role for the early detection of myocardial ischaemia and the assessment of the severity of ischaemic heart disease. Although stable patients with a healed myocardial infarction may have a relatively good prognosis, risk stratification in the predischarge period should be valuable for deciding upon appropriate management. In this respect, the presence of discordant BMIPP uptake relative to (201)Tl perfusion appears to be the best predictor of future cardiac events among all other cardiovascular imaging modalities. Since discordant BMIPP uptake correlates well with redistribution on stress (201)Tl imaging and perfusion-metabolism mismatch on positron emission tomography, it is considered that such BMIPP and (201)Tl discordance may identify a high-risk subgroup among patients with acute myocardial infarction. A BMIPP scan may reflect prior severe ischaemia after recovery of perfusion, the so-called "ischaemic memory". Gated BMIPP SPECT has been recently introduced for simultaneous assessment of myocardial metabolism and ventricular function. Such a new technique seems to be valuable for a better understanding of the pathophysiological state of heart failure and cardiomyopathy.

(+)-3-( sup 123 I)Iodo-MK-801: Synthesis and characterization of binding to the N-methyl-D-aspartate receptor complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ransom, R.W.; Wai-si Eng; Burns, H.D.

1990-01-01

Synthetic methods have been established for preparing high specific activity (+)-3-({sup 123}I)Iodo-MK-801 in high radiochemical yield. The binding of the radiotracer to rat cortical membranes has been examine to assess its potential use as an in vivo imaging agent for the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. Under the conditions of the assay, specific (+)-3-({sup 123}I)Iodo-MK-801 binding to membrane homogenates represented greater than 95% of the total binding. Several structurally distinct, noncompetitive NMDA receptor antagonists inhibited binding with potencies in accordance with their reported inhibitory activity at the receptor complex. The concentration of ({plus minus})-3-Iodo-MK-801 required to inhibit 50% of (+)-3-({supmore » 123}I)Iodo-MK-801 binding (IC{sub 50}) was 3.4 nM when using a low ionic strength assay buffer and 5.5 nM in a physiological buffer. In a thoroughly washed membrane preparation, (+)-3-({sup 123}I)Iodo-MK-801 binding was enhanced by L-glutamate and glycine at concentrations known to activate the NMDA receptor. The results indicate that (+)-3-({sup 123}I)Iodo-MK-801 specifically labels the NMDA receptor complex in rat brain membranes and the retention of high affinity under near physiological assay conditions suggests that it may be useful as a SPECT imaging agent for the receptor in vivo.« less

Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS).

PubMed

Mattner, Filomena; Mardon, Karine; Katsifis, Andrew

2008-04-01

The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([(123)I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [(123)I]-CLINDE. For in vivo studies, the rats were injected with [(123)I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [(123)I]-CLINDE binds with high affinity to PBBS, K(d) = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [(123)I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [(123)I]-CLINDE. [(123)I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT).

Seasonal influence on stimulated BAT activity in prospective trials: a retrospective analysis of BAT visualized on 18F-FDG PET-CTs and 123I-mIBG SPECT-CTs.

PubMed

Bahler, Lonneke; Deelen, Jan W; Hoekstra, Joost B; Holleman, Frits; Verberne, Hein J

2016-06-15

Retrospective studies have shown that outdoor temperature influences the prevalence of detectable brown adipose tissue (BAT). Prospective studies use acute cold exposure to activate BAT. In prospective studies, BAT might be preconditioned in winter months leading to an increased BAT response to various stimuli. Therefore the aim of this study was to assess whether outdoor temperatures and other weather characteristics modulate the response of BAT to acute cold. To assess metabolic BAT activity and sympathetic outflow to BAT, 64 (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) and 56 additional (123)I-meta-iodobenzylguanidine ((123)I-mIBG) single-photon emission computed tomography-CT (SPECT-CT) scans, respectively, of subjects participating in previously executed trials were retrospectively included. BAT activity was measured in subjects after an overnight fast, following 2 h of cold exposure (∼17°C). The average daytime outdoor temperatures and other weather characteristics were obtained from the Dutch Royal Weather Institute. Forty-nine subjects were BAT positive. One week prior to the scan, outdoor temperature was significantly lower in the BAT-positive group compared with the BAT-negative group. Higher outdoor temperatures on preceding days resulted in lower stimulated metabolic BAT activity and volume (all P < 0.01). Outdoor temperatures did not correlate with sympathetic outflow to BAT. In conclusion, outdoor temperatures influence metabolic BAT activity and volume, but not sympathetic outflow to BAT, in subjects exposed to acute cold. To improve the consistency of the findings of future BAT studies in humans and to exclude bias introduced by outdoor temperatures, these studies should be planned in periods of similar outdoor temperatures. Copyright © 2016 the American Physiological Society.

Comparison of brain serotonin transporter using [I-123]-ADAM between obese and non-obese young adults without an eating disorder

PubMed Central

Wu, Chih-Hsing; Chang, Chin-Sung; Yang, Yen Kuang; Shen, Lie-Hang; Yao, Wei-Jen

2017-01-01

Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46.0 ± 3.9%) and 10 age- and sex-matched non-obese controls (BMI: 20.3 ± 1.2 kg/m2, BF%: 20.6 ± 8.9%). All participants underwent SPECT at 10 min and 6 h after an injection of 200 MBq of [I-123]-ADAM. The SERT binding site (midbrain) was drawn with cerebellum normalization. The BF% and fat distribution were measured using dual-energy X-ray absorptiometry. The midbrain/cerebellum SERT binding ratios (2.49 ± 0.46 vs. 2.47 ± 0.47; p = 0.912) at 6 h were not significantly different between groups, nor was the distribution of the summed images at 10 min (1.36 ± 0.14 vs. 1.35 ± 0.11; p = 0.853). There were no significant correlations between midbrain/cerebellum SERT binding ratio and age, BMI, BF%, or fat distribution. No significant difference in SERT availability in the midbrain between morbidly obese and non-obese young adults without an eating disorder indicates an unmet need for investigating the role of cerebral serotonin in obesity. PMID:28182708

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.

PubMed

Joutsa, Juho; Johansson, Jarkko; Seppänen, Marko; Noponen, Tommi; Kaasinen, Valtteri

2015-07-01

Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2011-01-01

inhibitors, COX-2 inhibi- tors, other non - steroidal anti - inflammatory agents, opiate agonists, miscellaneous analgesics and antipyretics, thyroid...DA) similar to changes previously seen in PCB exposed adult non -human primates. To test that hypothesis we used [123I]β-CIT SPECT imaging to...adult non -human primates (Seegal et al., 1994a), also occur in occupationally exposed humans. In this study, we used in vivo molecular imaging of the

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

PubMed

Berendse, H W; Booij, J; Francot, C M; Bergmans, P L; Hijman, R; Stoof, J C; Wolters, E C

2001-07-01

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine.

PubMed

Kroiss, Alexander; Putzer, Daniel; Uprimny, Christian; Decristoforo, Clemens; Gabriel, Michael; Santner, Wolfram; Kranewitter, Christof; Warwitz, Boris; Waitz, Dietmar; Kendler, Dorota; Virgolini, Irene Johanna

2011-05-01

(68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001). Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.

Present assessment of myocardial viability by nuclear imaging.

PubMed

Saha, G B; MacIntyre, W J; Brunken, R C; Go, R T; Raja, S; Wong, C O; Chen, E Q

1996-10-01

Prospective delineation of viable from nonviable myocardium in patients with coronary artery disease in an important factor in deciding whether a patient should be revascularized or treated medically. Two common techniques--single-photon emission computed tomography (SPECT) and positron-emission computed tomography (PET)--are used in nuclear medicine using various radiopharmaceuticals for the detection of myocardial viability in patients. Thallium-201 (201Tl) and technetium-99m (99mTc)-sestamibi are the common radiopharmaceuticals used in different protocols using SPECT, whereas fluoride-18 (18F)-fluorodeoxyglucose (FDG) and rubidium-82 (82Rb) are most widely used in PET. The SPECT protocols involve stress/redistribution, stress/redistribution/reinjection, and rest/redistribution imaging techniques. Many studies have compared the results of 201Tl and (99mTc)-sestamibi SPECT with those of FDG PET; in some studies, concordant results have been found between delayed thallium and FDG results, indicating that 201Tl, although considered a perfusion agent, shows myocardial viability. Discordant results in a number of studies have been found between sestamibi and FDG, suggesting that the efficacy of sestamibi as a viability marker has yet to be established. Radiolabeled fatty acids such as iodine-123 (123I)-para-iodophenylpentadecanoic acid and carbon-11 (11C)-palmitic acid have been used for the assessment of myocardial viability with limited success. 11C-labeled acetate is a good marker of oxidative metabolism in the heart and has been used to predict the reversibility of wall motion abnormalities. (18F)-FDG is considered the marker of choice for myocardial viability, although variable results are obtained under different physiological conditions. Detection of myocardial viability can be greatly improved by developing new equipment and radiopharmaceuticals of better quality.

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

PubMed

Newberg, Andrew B; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S; Wintering, Nancy

2014-01-01

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to measure cerebral blood flow (CBF) and (123)I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Brain regions associated with cognitive impairment in patients with Parkinson disease: quantitative analysis of cerebral blood flow using 123I iodoamphetamine SPECT.

PubMed

Hattori, Naoya; Yabe, Ichiro; Hirata, Kenji; Shiga, Tohru; Sakushima, Ken; Tsuji-Akimoto, Sachiko; Sasaki, Hidenao; Tamaki, Nagara

2013-05-01

Cognitive impairment is a representative neuropsychiatric presentation that accompanies Parkinson disease (PD). The purpose of this study was to localize the cerebral regions associated with cognitive impairment in patients with PD using quantitative SPECT. Thirty-two patients with PD (mean [SD] age, 75 [8] years; 25 women; Hoehn-Yahr scores from 2 to 5) underwent quantitative brain SPECT using 123I iodoamphetamine. Parametric images of regional cerebral blood flow (rCBF) were spatially normalized to the standard brain atlas. First, voxel-by-voxel comparison between patients with PD with versus without cognitive impairment was performed to visualize overall trend of regional differences. Next, the individual quantitative rCBF values were extracted in representative cortical regions using a standard region-of-interest template to compare the quantitative rCBF values. Patients with cognitive impairment showed trends of lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices in the voxel-by-voxel analyses. Region-of-interest-based analysis demonstrated significantly lower rCBF in the bilateral anterior cingulate cortices (right, 25.8 [5.5] vs 28.9 [5.7] mL per 100 g/min, P < 0.05; left, 25.8 [5.8] vs 29.1 [5.7] mL per 100 g/min, P < 0.05) associated with cognitive impairment. Patients with cognitive impairment showed lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices. The results suggested dysexecutive function as an underlining mechanism of cognitive impairment in patients with PD.

Optimization of the reconstruction parameters in [123I]FP-CIT SPECT

NASA Astrophysics Data System (ADS)

Niñerola-Baizán, Aida; Gallego, Judith; Cot, Albert; Aguiar, Pablo; Lomeña, Francisco; Pavía, Javier; Ros, Domènec

2018-04-01

The aim of this work was to obtain a set of parameters to be applied in [123I]FP-CIT SPECT reconstruction in order to minimize the error between standardized and true values of the specific uptake ratio (SUR) in dopaminergic neurotransmission SPECT studies. To this end, Monte Carlo simulation was used to generate a database of 1380 projection data-sets from 23 subjects, including normal cases and a variety of pathologies. Studies were reconstructed using filtered back projection (FBP) with attenuation correction and ordered subset expectation maximization (OSEM) with correction for different degradations (attenuation, scatter and PSF). Reconstruction parameters to be optimized were the cut-off frequency of a 2D Butterworth pre-filter in FBP, and the number of iterations and the full width at Half maximum of a 3D Gaussian post-filter in OSEM. Reconstructed images were quantified using regions of interest (ROIs) derived from Magnetic Resonance scans and from the Automated Anatomical Labeling map. Results were standardized by applying a simple linear regression line obtained from the entire patient dataset. Our findings show that we can obtain a set of optimal parameters for each reconstruction strategy. The accuracy of the standardized SUR increases when the reconstruction method includes more corrections. The use of generic ROIs instead of subject-specific ROIs adds significant inaccuracies. Thus, after reconstruction with OSEM and correction for all degradations, subject-specific ROIs led to errors between standardized and true SUR values in the range [‑0.5, +0.5] in 87% and 92% of the cases for caudate and putamen, respectively. These percentages dropped to 75% and 88% when the generic ROIs were used.

Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

PubMed

Furuta, Akihiro; Onishi, Hideo; Amijima, Hizuru

2018-06-01

This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123 I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

Micro–Single-Photon Emission Computed Tomography Image Acquisition and Quantification of Sodium-Iodide Symporter–Mediated Radionuclide Accumulation in Mouse Thyroid and Salivary Glands

PubMed Central

Brandt, Michael P.; Kloos, Richard T.; Shen, Daniel H.; Zhang, Xiaoli; Liu, Yu-Yu

2012-01-01

Background Micro–single-photon emission computed tomography (SPECT) provides a noninvasive way to evaluate the effects of genetic and/or pharmacological modulation on sodium-iodide symporter (NIS)–mediated radionuclide accumulation in mouse thyroid and salivary glands. However, parameters affecting image acquisition and analysis of mouse thyroids and salivary glands have not been thoroughly investigated. In this study, we investigated the effects of region-of-interest (ROI) selection, collimation, scan time, and imaging orbit on image acquisition and quantification of thyroidal and salivary radionuclide accumulation in mice. Methods The effects of data window minima and maxima on thyroidal and salivary ROI selection using a visual boundary method were examined in SPECT images acquired from mice injected with 123I NaI. The effects of collimation, scan time, and imaging orbit on counting linearity and signal intensity were investigated using phantoms filled with various activities of 123I NaI or Tc-99m pertechnetate. Spatial resolution of target organs in whole-animal images was compared between circular orbit with parallel-hole collimation and spiral orbit with five-pinhole collimation. Lastly, the inter-experimental variability of the same mouse scanned multiple times was compared with the intra-experimental variability among different mice scanned at the same time. Results Thyroid ROI was separated from salivary glands by empirically increasing the data window maxima. Counting linearity within the range of 0.5–14.2 μCi was validated by phantom imaging using single- or multiple-pinhole collimators with circular or spiral imaging orbit. Scanning time could be shortened to 15 minutes per mouse without compromising counting linearity despite proportionally decreased signal intensity. Whole-animal imaging using a spiral orbit with five-pinhole collimators achieved a high spatial resolution and counting linearity. Finally, the extent of inter-experimental variability of NIS-mediated radionuclide accumulation in the thyroid and salivary glands by SPECT imaging in the same mouse was less than the magnitude of variability among the littermates. Conclusions The impacts of multiple variables and experimental designs on micro-SPECT imaging and quantification of radionuclide accumulation in mouse thyroid and salivary glands can be minimized. This platform will serve as an invaluable tool to screen for pharmacologic reagents that differentially modulate thyroidal and salivary radioiodine accumulation in preclinical mouse models. PMID:22540327

[A case study of BRON (cough suppressant) tablet dependence--its social psychiatric and biological aspects].

PubMed

Kitabayashi, Y; Ueda, H; Narumoto, J; Kita, H; Nakamura, K; Tsuchida, H; Tani, N; Fukui, K

2000-10-01

A case of BRON tablet dependence is demonstrated. BRON is an over-the-counter (OTC) cough suppressant, which contains methylephedrine, dihydrocodeine, chlorpheniramine and caffeine. He took BRON tablet for the first time at the age of 16. In progress, he developed psychomotor excitement twice and finally manifested amotivational syndrome 3 years later from his first use. Longitudinal 123I-IMP SPECT (autoradiography method) findings demonstrated diffuse cerebral blood flow (CBF) decrease and relative hyperactivity in the lower frontal lobe. Diffuse decreased regional CBF, which was unchanged through its course for about 4 months, may show irreversible brain damage due to chronic BRON abuse. The findings of relative hyperactivity in the lower frontal lobe (orbitofrontal lobe) may reflect "craving for BRON" based on abnormal dopaminergic neural system activity. Based on the evidence that orbitofrontal hyperactivity is also seen in cases of cocaine abuse, methylephedrine, which is a cocaine-like central nervous system stimulant, may play the main role in BRON dependence formation. In Japan, BRON syrup abuse and dependence were in fashion for youth in 1980s. After the legal regulation of the market in 1988, it has gone out of fashion. While it is still easy to acquire OTC cough suppressant, reports of BRON tablet abuse and dependence are quite rare through 1980s and 1990s. This case suggests that BRON tablet abuse also could lead to dependence and come into new vogue for youth in the future. We should pay attention to the trend of OTC cough suppressant abuse and may need to regulate the market by law more severely.

Regional cerebral blood flow and abnormal eating behavior in Prader-Willi syndrome.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Fukuda, Hiroshi; Mori, Etsuro

2013-05-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Preclinical properties and human in vivo assessment of 123 I-ABC577 as a novel SPECT agent for imaging amyloid-β

PubMed Central

Okumura, Yuki; Kobayashi, Ryohei; Onishi, Takako; Shoyama, Yoshinari; Barret, Olivier; Alagille, David; Jennings, Danna; Marek, Kenneth; Seibyl, John; Tamagnan, Gilles; Tanaka, Akihiro; Shirakami, Yoshifumi

2016-01-01

Abstract Non-invasive imaging of amyloid-β in the brain, a hallmark of Alzheimer’s disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer 123 I-ABC577 as a potential imaging biomarker for amyloid-β in the brain. The radio-iodinated imidazopyridine derivative 123 I-ABC577 was designed as a candidate for a novel amyloid-β imaging agent. The binding affinity of 123 I-ABC577 for amyloid-β was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer’s disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of 123 I-ABC577. Furthermore, to validate 123 I-ABC577 as a biomarker for Alzheimer’s disease, we performed a clinical study to compare the brain uptake of 123 I-ABC577 in three patients with Alzheimer’s disease and three healthy control subjects. 123 I-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, 123 I-ABC577 showed high binding affinity for amyloid-β and desirable pharmacokinetics in the preclinical studies. In the clinical study, 123 I-ABC577 was an effective marker for discriminating patients with Alzheimer’s disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer’s disease, 123 I-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by ∼60% in patients with Alzheimer’s disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer’s disease showed minimal 123 I-ABC577 retention in the white matter. These observations indicate that 123 I-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-β in the human brain. The availability of an amyloid-β tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer’s disease. PMID:26490333

Loss of Substantia Nigra Hyperintensity at 3.0-T MR Imaging in Idiopathic REM Sleep Behavior Disorder: Comparison with 123I-FP-CIT SPECT.

PubMed

Bae, Yun Jung; Kim, Jong-Min; Kim, Kyeong Joon; Kim, Eunhee; Park, Hyun Soo; Kang, Seo Young; Yoon, In-Young; Lee, Jee-Young; Jeon, Beomseok; Kim, Sang Eun

2018-04-01

Purpose To examine whether the loss of nigral hyperintensity (NH) on 3.0-T susceptibility-weighted (SW) magnetic resonance (MR) images can help identify high synucleinopathy risk in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Materials and Methods Between March 2014 and April 2015, 18 consecutively recruited patients with iRBD were evaluated with 3.0-T SW imaging and iodine 123-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ( 123 I-FP-CIT) single photon emission computed tomography and compared with 18 healthy subjects and 18 patients with Parkinson disease (PD). Two readers blinded to clinical diagnosis independently assessed the images. 123 I-FP-CIT uptake ratios were compared by using the Kruskal-Wallis test, and intra- and interobserver agreements were assessed with the Cohen κ. The synucleinopathy conversion according to NH status was evaluated in patients with iRBD after follow-up. Results NH was intact in seven patients with iRBD and lost in 11. The 123 I-FP-CIT uptake ratios were comparable between those with intact NH (mean, 3.22 ± 0.47) and healthy subjects (mean, 3.37 ± 0.47) (P = .495). The 123 I-FP-CIT uptake ratios in the 11 patients with iRBD and NH loss (mean, 2.48 ± 0.44) were significantly lower than those in healthy subjects (mean, 3.37 ± 0.47; P < .001) but higher than those in patients with PD (mean, 1.80 ± 0.33; P < .001). The intra- and interobserver agreements were excellent (κ > 0.9). Five patients with iRBD and NH loss developed symptoms of parkinsonism or dementia 18 months after neuroimaging. Conclusion NH loss at 3.0-T SW imaging may be a promising marker for short-term synucleinopathy risk in iRBD. © RSNA, 2017 Online supplemental material is available for this article.

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology

PubMed Central

Yoshinaga, Keiichiro

2010-01-01

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. 123I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) 123I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds. PMID:21082300

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator.

PubMed

King, Michael A; Mukherjee, Joyeeta M; Könik, Arda; Zubal, I George; Dey, Joyoni; Licho, Robert

2016-02-01

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 × 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

A role for locus coeruleus in Parkinson tremor

PubMed Central

Isaias, Ioannis U.; Marzegan, Alberto; Pezzoli, Gianni; Marotta, Giorgio; Canesi, Margherita; Biella, Gabriele E. M.; Volkmann, Jens; Cavallari, Paolo

2012-01-01

We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor. PMID:22287946

[Detection of cerebral hypoperfusion using single photon emission computed tomography image analysis and statistical parametric mapping in patients with Parkinson's disease or progressive supranuclear palsy].

PubMed

Harada, Kengo; Saeki, Hiroshi; Matsuya, Eiji; Okita, Izumi

2013-11-01

We carried out differential diagnosis of brain blood flow images using single-photon emission computed tomography (SPECT) for patients with Parkinson's disease (PD) or progressive supranuclear paralysis (PSP) using statistical parametric mapping (SPM) and to whom we had applied anatomical standardization. We studied two groups and compared brain blood flow images using SPECT (N-isopropyl-4-iodoamphetamine [(123)I] hydrochloride injection, 222 MGq dosage i.v.). A total of 27 patients were studied using SPM: 18 with PD and 9 with PSP; humming bird sign on MRI was from moderate to medium. The decline of brain bloodstream in the PSP group was more notable in the midbrain, near the domain where the humming bird sign was observable, than in the PD group. The observable differences in brain bloodstream decline in the midbrain of PSP and PD patients suggest the potential usefulness of this technique's clinical application to distinction diagnosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langen, K.J.; Roosen, N.; Coenen, H.H.

SPECT studies with L-3-(123I)iodo-alpha-methyl tyrosine (IMT) were carried out in 10 patients with different types of brain tumors--first under fasting conditions (basal) and a week later during intravenous infusion of a mixture of naturally-occurring L-amino acids (AA load). An uptake index (UI) was calculated by dividing tissue count rates by the integral of plasma count rates. The UI decreased by 45.6% {plus minus} 15.4% (n = 10, p less than 0.001) for normal brain and by 53.2% {plus minus} 14.1% for gliomas (n = 5, p less than 0.01) during AA load compared to basal conditions, while two meningiomas andmore » a metastasis showed only a minor decrease (23.9 {plus minus} 5.7%, n.s.). Two pituitary adenomas could not be delineated on the SPECT scans. These data indicate that IMT competes with naturally-occurring L-amino acids for transport into normal brain and gliomas. Transport characteristics of IMT into tumors of nonglial origin appear to be different from those of gliomas. For both types of tumors, it is advisable to perform IMT-SPECT under fasting conditions.« less

Clinical application of arterial spin-labeling MR imaging in patients with carotid stenosis: quantitative comparative study with single-photon emission CT.

PubMed

Uchihashi, Y; Hosoda, K; Zimine, I; Fujita, A; Fujii, M; Sugimura, K; Kohmura, E

2011-09-01

Arterial spin-labeling is an emerging technique for noninvasive measurement of cerebral perfusion, but concerns remain regarding the reliability of CBF quantification and clinical applications. Recently, an ASL implementation called QUASAR was proposed, and it was shown to have good reproducibility of CBF assessment in healthy volunteers. This study aimed to determine the utility of QUASAR for CBF assessment in patients with cerebrovascular diseases. Twenty patients with carotid stenosis underwent CBF quantification by ASL (QUASAR) within 3 days of performance of (123)I-iodoamphetamine-SPECT. CVR to acetazolamide also was assessed by ASL and SPECT. In surgically treated patients, the respective scans before and after the procedures were compared. Regional CBF and CVR values measured by ASL were significantly correlated and agreed with those measured by SPECT (r(s) = 0.92 and 0.88, respectively). A Bland-Altman plot demonstrated good agreement between 2 methods in terms of CBF quantification. Furthermore, ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion, equivalent to SPECT. However, ASL tended to overestimate CBF values especially in high-perfusion regions. ASL perfusion MR imaging is clinically applicable and can be an alternative method for CBF assessment in patients with cerebrovascular diseases.

Role of (123)I-Iobenguane Myocardial Scintigraphy in Predicting Short-term Left Ventricular Functional Recovery: An Interesting Image.

PubMed

Feola, Mauro; Chauvie, Stephane; Biggi, Alberto; Testa, Marzia

2015-01-01

(123)I-iobenguane myocardial scintigraphy (MIBG) has been shown to be a predictor of sudden cardiac mortality in patients with heart failure. One patient with recent anterior myocardial infarction (MI) treated with coronary angioplasty and having left ventricular ejection fraction (LVEF) of 30% underwent early MIBG myocardial scintigraphy/tetrofosmin single-photon emission computed tomography (SPECT) in order to help evaluate his eligibility for implantable cardioverter defibrillator (ICD). The late heart/mediastinum (H/M) ratio was calculated to be 1.32% and the washout rate was 1%. At 40-day follow-up after angioplasty, LVEF proved to be 32%, New York Heart Association (NYHA) class was still II-III, and an ICD was placed in order to reduce mortality from ventricular arrhythmias. MIBG myocardial scintigraphy might be a promising method for evaluating left ventricular recovery in post-MI patients.

[Changes in visual event-related potentials and SPECT in dissociative amnesia].

PubMed

Kurita, Akira; Yonezawa, Jin; Suzuki, Masahiko; Kawaguchi, Sachiko; Ito, Yasuhiko; Inoue, Kiyoharu

2004-01-01

A 29-year-old man was admitted because of sudden onset of retrograde amnesia. The patient was unable to recall events having occurred during the past 2 years. The impairment was especially serious with regard to personal memories during the 5 months prior to admission, while he had first been working as a full-time employee under stressful circumstance. A diagnosis of dissociative amnesia was made on the basis of absence of any systemic or neurological diseases that could cause amnesia, the inadaptable character of the patient, the nature of amnesia, and presence of stressful condition possibly related to the amnesia. Visual event-related potential (ERP) studies recorded with human face discrimination tasks demonstrated a P3a wave in response to a face of his superior in the office, whom he said that he had never seen before. The similar P3a wave was observed in response to a face quite familiar to the patient, his mother, but not to a face "truly" unknown to him. These findings suggest that the visual memory of his superior's face exists in the brain, but the patient is unable to retrieve it by some psychogenic mechanism. 131I-IMP SPECT revealed decreased perfusion in the left medial temporal lobe and the basal forebrain, suggesting the association between dissociative amnesia and focal brain dysfunction. While dissociative amnesia has been understood as psychogenic nature, both ERPs and SPECT are quite important tools to understand the association between the psychological phenomenon and biological changes of the brain in this disorder.

Clinical Comparison of 99mTc Exametazime and 123I Ioflupane SPECT in Patients with Chronic Mild Traumatic Brain Injury

PubMed Central

Newberg, Andrew B.; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S.; Wintering, Nancy

2014-01-01

Background This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Methods and Findings Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both 99mTc exametazime to measure cerebral blood flow (CBF) and 123I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Conclusions Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario. PMID:24475210

Global scaling for semi-quantitative analysis in FP-CIT SPECT.

PubMed

Kupitz, D; Apostolova, I; Lange, C; Ulrich, G; Amthauer, H; Brenner, W; Buchert, R

2014-01-01

Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

(123)I-BZA2 as a melanin-targeted radiotracer for the identification of melanoma metastases: results and perspectives of a multicenter phase III clinical trial.

PubMed

Cachin, Florent; Miot-Noirault, Elisabeth; Gillet, Brigitte; Isnardi, Vanina; Labeille, Bruno; Payoux, Pierre; Meyer, Nicolas; Cammilleri, Serge; Gaudy, Caroline; Razzouk-Cadet, Micheline; Lacour, Jean Philippe; Granel-Brocard, Florence; Tychyj, Christelle; Benbouzid, Fathalah; Grange, Jean Daniel; Baulieu, Françoise; Kelly, Antony; Merlin, Charles; Mestas, Danielle; Gachon, Françoise; Chezal, Jean Michel; Degoul, Françoise; D'Incan, Michel

2014-01-01

Our group has developed a new radiopharmaceutical, (123)I - N-(2-diethylaminoethyl)-2-iodobenzamide ((123)I-BZA2), a benzamide derivative able to bind to melanin pigment in melanoma cells. In a prospective and multicentric phase III clinical study, the value of (18)F-FDG PET/CT and (123)I-BZA2 scintigraphy was compared for melanoma staging. Patients with a past history of cutaneous or ocular melanoma were included from 8 hospitals. (18)F-FDG imaging was performed according to a standard PET protocol. Whole-body, static planar, and SPECT/CT (if available) images were acquired 4 h after injection of a 2 MBq/kg dose of (123)I-BZA2. (18)F-FDG and (123)I-BZA2 sensitivity and specificity for the diagnosis of melanoma metastasis were calculated and compared on both a lesion basis and a patient basis. True-positive and true-negative lesion status was determined after 6 mo of clinical follow-up or according to lesion biopsies (if available). Melanin content in biopsies was evaluated with the standard Fontana-Masson silver method and was correlated with (123)I-BZA2 uptake. Based on statistical analysis, the number of inclusions was estimated at 186. In all, 87 patients were enrolled from 2008 to 2010. Of these, 45 (52%) had metastases. A total of 338 imaging abnormalities were analyzed; 86 lesions were considered metastases, and 20 of 25 lesion biopsies found melanoma metastases. In a patient-based analysis, the sensitivity of (18)F-FDG for diagnosis of melanoma metastases was higher than that of (123)I-BZA2, at 87% and 39%, respectively (P < 0.05). For specificity, (18)F-FDG and (123)I-BZA2 were not statistically different, at 78% and 94%, respectively. In a lesion-based analysis, the sensitivity of (18)F-FDG was statistically higher than that of (123)I-BZA2 (80% vs. 23%, P < 0.05). The specificity of (18)F-FDG was lower than that of (123)I-BZA2 (54% vs. 86%, P < 0.05). According to biopsy analysis, only 9 of 20 metastatic lesions (45%) were pigmented with high melanin content. (123)I-BZA2 imaging was positive for 6 of 8 melanin-positive lesions, fairly positive for 3 of 10 melanin-negative lesions, and negative for 7 of 10 melanin-negative lesions. The sensitivity and specificity of (123)I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively. Because of a low (123)I-BZA2 sensitivity, this clinical trial was prematurely closed after 87 patients had been included. This study confirms the value of (18)F-FDG PET/CT for melanoma staging and strengthens the high accuracy of (123)I-BZA2 for diagnosis of melanin-positive metastatic melanoma. Moreover, benzamide derivatives radiolabeled with therapeutic radionuclide may offer a new strategy for the treatment of metastatic melanoma patients harboring melanin-positive metastases.

Pinhole Micro-SPECT/CT for Noninvasive Monitoring and Quantitation of Oncolytic Virus Dispersion and Percent Infection in Solid Tumors

PubMed Central

Penheiter, Alan R.; Griesmann, Guy E.; Federspiel, Mark J.; Dingli, David; Russell, Stephen J.; Carlson, Stephanie K.

2011-01-01

The purpose of our study was to validate the ability of pinhole micro-single-photon emission computed tomography/computed tomography (SPECT/CT) to 1) accurately resolve the intratumoral dispersion pattern and 2) quantify the infection percentage in solid tumors of an oncolytic measles virus encoding the human sodium iodide symporter (MV-NIS). NIS RNA level and dispersion pattern were determined in control and MV-NIS infected BxPC-3 pancreatic tumor cells and mouse xenografts using quantitative, real-time, reverse transcriptase, polymerase chain reaction, autoradiography, and immunohistochemistry (IHC). Mice with BxPC-3 xenografts were imaged with 123I or 99TcO4 micro-SPECT/CT. Tumor dimensions and radionuclide localization were determined with imaging software. Linear regression and correlation analyses were performed to determine the relationship between tumor infection percentage and radionuclide uptake (% injected dose per gram) above background and a highly significant correlation was observed (r2 = 0.947). A detection threshold of 1.5-fold above the control tumor uptake (background) yielded a sensitivity of 2.7% MV-NIS infected tumor cells. We reliably resolved multiple distinct intratumoral zones of infection from noninfected regions. Pinhole micro-SPECT/CT imaging using the NIS reporter demonstrated precise localization and quantitation of oncolytic MV-NIS infection and can replace more time-consuming and expensive analyses (eg, autoradiography and IHC) that require animal sacrifice. PMID:21753796

I-123 - FP-CIT pharmacokinetics and dosimetry show great potential for the evaluation of dopamine transporter system in clinical routine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costa, D.C.; Walker, S.; Waddington, W.

1996-05-01

FP-CIT is a N-fluoropropyl analogue of the [2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane] which has been labelled with I-123 and developed as a new marker of the pre-synaptic dopamine transporter system. Its selective uptake in the striatum of non-human primates and human volunteers has been reported with advantageous faster brain kinetics than {beta}-CIT. In this pilot work we studied the whole body imaging kinetics of FP-CIT in one normal volunteer - NV (5, 60, 100, 360 minutes and 24 hours post-injection for 20 minutes each) and a drug-free patient with well established Parkinson`s disease - PD (100 minutes) after intravenous injection of 111 MBq. Bothmore » subjects had high resolution brain SPECT at 35 minutes and 3.5 hours post-injection. Percent of whole body uptake (geometric mean of anterior and posterior projections) in different organs, including total brain and basal ganglia shows rapid clearance from blood during the first hour with no significant change from 100 minutes to 24 hours. The basal ganglia uptake is approximately 0.4% of total body from 100 minutes onwards. Striatal uptake (ratio to frontal cortex) is different between subjects, mainly at 3.5 hours and more marked in the putamen: Calculated dosimetry (mSv/MBq) showed E.D.E.-0.034, and total doses to whole body - 0.01, total brain - 0.017, basal ganglia - 0.155, small intestine - 0.06, urinary bladder - 0.05 and liver - 0.03. These data confirm that FP-CIT has acceptable dosimetry with good pharmacokinetics enabling the study of pre-synaptic dopamine transport system in nigrostriatal degeneration with clinical SPECT at 3-4 hrs p.i.« less

High affinity dopamine D2 receptor radioligands. 3. [[sup 123]I] and [[sup 125]I]epidepride: In vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kessler, R.M.; Votaw, J.R.; Schmidt, D.E.

1993-01-01

Studies of [[sup 123]I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [[sup 123]I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [[sup 123]I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [[sup 123]I]epidepridemore » is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies with [[sup 125]I]epidepride using rat striatum revealed a K[sub D] of 46 pM and B[sub max] of 33 pmol/g tissue at 37[degrees]C, while at 25[degrees]C the K[sub D] was 25 pM and the B[sub max] 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37[degrees]C of 15 min and 79--90 min at 25[degrees]C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25[degrees]C. Increasing in vitro incubation temperature from 25 to 37[degrees]C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37[degrees]C compared to in vivo binding. The results of this study indicate that [[sup 123]I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man. 34 refs., 4 figs.« less

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM.

PubMed

Donnemiller, E; Brenneis, C; Wissel, J; Scherfler, C; Poewe, W; Riccabona, G; Wenning, G K

2000-09-01

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Evaluation of Parkinson's disease by neuromelanin-sensitive magnetic resonance imaging and 123I-FP-CIT SPECT.

PubMed

Kuya, Keita; Ogawa, Toshihide; Shinohara, Yuki; Ishibashi, Mana; Fujii, Shinya; Mukuda, Naoko; Tanabe, Yoshio

2018-05-01

Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and 123 I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson's disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin-positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc volume and SBR were also calculated. We evaluated the relationship between the UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume showed a significant correlation with the SBR. The AIs of them also showed a significant correlation. Both the mean of the bilateral SBR and the mean of the bilateral SNc volume showed significant negative correlations with the UPDRS III score. However, the correlation between the SBR and the UPDRS III score was stronger than that between the SNc volume and the UPDRS III score. Conclusion Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that DaTSCAN is more suitable for the evaluation of the clinical motor severity and would be more useful for the management of PD patients than NmMRI.

Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

PubMed

Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

2011-05-01

In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG scintigraphy is likely to significantly increase TA in differentiating PD from APD. The differential diagnosis of degenerative parkinsonism may thus be facilitated.

Development of a Germanium Small-Animal SPECT System

NASA Astrophysics Data System (ADS)

Johnson, Lindsay C.; Ovchinnikov, Oleg; Shokouhi, Sepideh; Peterson, Todd E.

2015-10-01

Advances in fabrication techniques, electronics, and mechanical cooling systems have given rise to germanium detectors suitable for biomedical imaging. We are developing a small-animal SPECT system that uses a double-sided Ge strip detector. The detector's excellent energy resolution may help to reduce scatter and simplify processing of multi-isotope imaging, while its ability to measure depth of interaction has the potential to mitigate parallax error in pinhole imaging. The detector's energy resolution is <; 1% FWHM at 140 keV and its spatial resolution is approximately 1.5 mm FWHM. The prototype system described has a single-pinhole collimator with a 1-mm diameter and a 70-degree opening angle with a focal length variable between 4.5 and 9 cm. Phantom images from the gantry-mounted system are presented, including the NEMA NU-2008 phantom and a hot-rod phantom. Additionally, the benefit of energy resolution is demonstrated by imaging a dual-isotope phantom with 99mTc and 123I without cross-talk correction.

Core Binding Site of a Thioflavin-T-Derived Imaging Probe on Amyloid β Fibrils Predicted by Computational Methods.

PubMed

Kawai, Ryoko; Araki, Mitsugu; Yoshimura, Masashi; Kamiya, Narutoshi; Ono, Masahiro; Saji, Hideo; Okuno, Yasushi

2018-05-16

Development of new diagnostic imaging probes for Alzheimer's disease, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) probes, has been strongly desired. In this study, we investigated the most accessible amyloid β (Aβ) binding site of [ 123 I]IMPY, a Thioflavin-T-derived SPECT probe, using experimental and computational methods. First, we performed a competitive inhibition assay with Orange-G, which recognizes the KLVFFA region in Aβ fibrils, suggesting that IMPY and Orange-G bind to different sites in Aβ fibrils. Next, we precisely predicted the IMPY binding site on a multiple-protofilament Aβ fibril model using computational approaches, consisting of molecular dynamics and docking simulations. We generated possible IMPY-binding structures using docking simulations to identify candidates for probe-binding sites. The binding free energy of IMPY with the Aβ fibril was calculated by a free energy simulation method, MP-CAFEE. These computational results suggest that IMPY preferentially binds to an interfacial pocket located between two protofilaments and is stabilized mainly through hydrophobic interactions. Finally, our computational approach was validated by comparing it with the experimental results. The present study demonstrates the possibility of computational approaches to screen new PET/SPECT probes for Aβ imaging.

Myocardial impairment detected by late gadolinium enhancement in hypertrophic cardiomyopathy: comparison with 99mTc-MIBI/tetrofosmin and 123I-BMIPP SPECT.

PubMed

Hashimura, Hiromi; Kiso, Keisuke; Yamada, Naoaki; Kono, Atsushi; Morita, Yoshiaki; Fukushima, Kazuto; Higashi, Masahiro; Noguchi, Teruo; Ishibashi-Ueda, Hatsue; Naito, Hiroaki; Sugimura, Kazuro

2013-06-17

Myocardial fibrosis is considered to be an important factor in myocardial dysfunction and sudden cardiac death in hypertrophic cardiomyopathy (HCM). The purpose of this study was to compare myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac MRI with myocardial perfusion and fatty acid metabolism assessed by single photon emission computed tomography in HCM. We retrospectively evaluated 20 consecutive HCM patients (female, 7; mean age, 53.4 years) who underwent LGE, technetium-99m methoxyisobutylisonitrile/tetrofosmin (99mTc-MIBI/tetrofosmin), and iodine-123 beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging. We calculated the myocardium-to-lumen signal ratio (M/L) for LGE in 17 segments based on the American Heart Association statement. Scoring of 99mTc-MIBI/tetrofosmin (PI) and 123I-BMIPP (BM) was performed for each segment using a 5-point scale (0, normal; 4, highly decreased). Nineteen of 20 patients (95%) and 153 of 340 segments (45%) showed LGE. M/Ls were 0.42±0.16, 0.55±0.17, and 0.65±0.24 in PI0/BM0, PI0/BM1-4 and PI1-4/BM1-4, respectively. All M/Ls were significantly higher than that of a normal control (0.34±0.14) (p<0.001). Myocardial fibrosis in HCM can occur despite normal perfusion and fatty acid metabolism, and is more strongly associated with disorders of fatty acid metabolism than with perfusion abnormalities. M/L may be a useful indicator of disease severity.

A radioisotope based methodology for plant-fungal interactions in the rhizosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisenberger, A. G.; Bonito, G.; Lee, S.

In plant ecophysiology research there is interest in studying the biology of the rhizosphere because of its importance in plant nutrient-interactions. The rhizosphere is the zone of soil surrounding a plant's root system where microbes (such as fungi) are influenced by the root and the roots by the microbes. We are investigating a methodology for imaging the distribution of molecular compounds of interest in the rhizosphere without disturbing the root or soil habitat. Our intention is to develop a single photon emission computed tomography (SPECT) system (PhytoSPECT) to image the bio-distribution of fungi in association with a host plant's roots.more » The technique we are exploring makes use of radioactive isotopes as tracers to label molecules that bind to fungal-specific compounds of interest and to image the fungi distribution in the plant and/or soil. We report on initial experiments designed to test the ability of fungal-specific compounds labeled with an iodine radioisotope that binds to chitin monomers (N-acetylglucosamine). Chitin is a compound not found in roots but in fungal cell walls. We will test the ability to label the compound with radioactive isotopes of iodine ({sup 125}I, and {sup 123}I).« less

[SCA6 presenting parkinsonism without ataxia--A case report].

PubMed

Takeshima, Shinichi; Takeda, Ikuko; Kobatake, Keitaro; Yamashita, Toru; Abe, Koji; Kuriyama, Masaru

2015-01-01

A 57-year-old man was admitted to our hospital because of bradykinesia. He was diagnosed with Parkinson disease (Hoehn and Yahr grade 2) and administered levodopa at the maximum dose of 800 mg. However, his condition did not improve. While his symptoms were responsive to levodopa therapy, the sensitivity to the drug was poor. Brain MRI revealed atrophy of the upper vermis and cerebral hemispheres, and brain SPECT revealed low perfusion in both parietal lobes. I(123)-metaiodobenzylguanidine scintigraphy showed a decrease in the heart/mediastinum ratio. Striatal dopamine transporter (DAT) density was evaluated using I(123)-FP-CIT. The patient showed moderately reduced DAT density, which suggested nigrostriatal dopaminergic damage. His mother was found to have pure cerebellar ataxia without parkinsonism, and her two siblings also had celebellar type of multiple system atrophy (MSA-C) and progressive supranuclear palsy, respectively. Genetic testing revealed that the patient, his mother and the uncle with MSA-C had spinocerebellar ataxia type 6 (SCA6). SCA6 presenting parkinsonism without ataxia is very rare and important for the pathomechanism of disease.

In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting

PubMed Central

Hall, Håkan; Velikyan, Irina; Blom, Elisabeth; Ulin, Johan; Monazzam, Azita; Påhlman, Lars; Micke, Patrick; Wanders, Alkwin; McBride, William; Goldenberg, David M.; Långström, Bengt

2012-01-01

The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with 67Ga or 68Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of 67/68Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using 67Ga and SPECT or 68Ga and PET. PMID:23133809

Dopamine D2 receptor status assessed by IBZM SPECT - A sensitive indicator for cerebral hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tatsch, K.; Schwarz, J.; Welz, A.

1995-05-01

The striatum is highly sensitive to tissue hypoxia. Thus, it may be suggested that cerebral hypoxia could affect the integrity of the striatal receptor system. Purpose of the current SPECT investigations with IBZM was to evaluate whether hypoxic conditions cause detectable changes in the D2 receptor status. 25 controls and 30 pts with history of cerebral hypoxia (resuscitation after cardiac arrest: n=19, CABG surgery under cardiopulmonary bypass: n=11) were investigated with SPECT 2h p.i. of 185 MBq I-123 IBZM. For semiquant, evaluation transverse slices corrected for attenuation were used to calculate striatal to frontal cortex (S/FC) ratios. In 13/19 ptsmore » with cerebral hypoxia due to cardiac arrest IBZM binding was severely reduced after successful resuscitation. 7 died, 5 were in a vegetative state, 1 remained severely disabled. In 6/19 S/FC ratios were normal/mildly reduced, 2 of them had a good outcome, 4 were moderatley disabled. In pts with CABG IBZM binding was preoperatively normal. After hypoxia due to cardiac surgery striatal S/FC ratios decreased slightly, persisting on this level even 6 months after surgery. Neuropsychological/psychiatric testing showed only minor or transient changes in this group of patients. The striatal D2 receptor status seems to be a sensitive indicator for cerebral hypoxia. After hypoxia due to cardiac arrest IBZM results well correlate (in contrast to morphological or SEP findings) with the clinical outcome and thus may serve as early predictor of the individual prognosis. The moderate decline in IBZM binding following CABG surgery suggests mild cerebral hypoxia despite of protective hypothermia. Sensitively indicating cerebral hypoxia changes in the D2 receptor status assessed by IBZM SPECT may serve as a valuable diagnostic tool for testing neuroprotective drugs or modified surgical techniques.« less

Synthesis and Preclinical Evaluation of Radioiodinated Hypericin Dicarboxylic Acid as a Necrosis Avid Agent in Rat Models of Induced Hepatic, Muscular, and Myocardial Necroses.

PubMed

Li, Jindian; Zhang, Jian; Yang, Shengwei; Jiang, Cuihua; Zhang, DongJian; Jin, Qiaomei; Wang, Qin; Wang, Cong; Ni, Yicheng; Yin, Zhiqi; Song, Shaoli

2016-01-04

Myocardial infarction (MI) leads to substantial morbidity and mortality around the world. Accurate assessment of myocardial viability is essential to assist therapies and improve patient outcomes. (131)I-hypericin dicarboxylic acid ((131)I-HDA) was synthesized and evaluated as a potential diagnostic agent for earlier assessment of myocardium viability compared to its preceding counterpart (131)I-hypericin ((131)I-Hyp) with strong hydrophobic property, long plasma half-life, and high uptake in mononuclear phagocyte system (MPS). Herein, HDA was synthesized and characterized, and self-aggregation constant Kα was analyzed by spectrophotometry. Plasma half-life was determined in healthy rats by γ-counting. (131)I-HDA and (131)I-Hyp were prepared with iodogen as oxidant. In vitro necrosis avidity of (131)I-HDA and (131)I-Hyp was evaluated in necrotic cells induced by hyperthermia. Biodistribution was determined in rat models of induced necrosis using γ-counting, autoradiography, and histopathology. Earlier imaging of necrotic myocardium to assess myocardial viability was performed in rat models of reperfused myocardium infarction using single photon emission computed tomography/computed tomography (SPECT/CT). As a result, the self-aggregation constant Kα of HDA was lower than that of Hyp (105602 vs 194644, p < 0.01). (131)I-HDA displayed a shorter blood half-life compared with (131)I-Hyp (9.21 vs 31.20 h, p < 0.01). The necrotic-viable ratio in cells was higher with (131)I-HDA relative to that with (131)I-Hyp (5.48 vs 4.63, p < 0.05). (131)I-HDA showed a higher necrotic-viable myocardium ratio (7.32 vs 3.20, p < 0.01), necrotic myocardium-blood ratio (3.34 vs 1.74, p < 0.05), and necrotic myocardium-lung ratio (3.09 vs 0.61, p < 0.01) compared with (131)I-Hyp. (131)I-HDA achieved imaging of necrotic myocardium at 6 h postinjection (p.i.) with SPECT/CT, earlier than what (131)I-Hyp did. Therefore, (131)I-HDA may serve as a promising necrosis-avid diagnostic agent for earlier imaging of necrotic myocardium compared with (131)I-Hyp. This may support further development of radiopharmaceuticals ((123)I and (99m)Tc) based on HDA for SPECT/CT of necrotic myocardium.

Pyrrolo isoquinolines

DOEpatents

Goodman, Mark M.; Shi, Bing Z.

2000-01-01

Compounds of the formula: ##STR1## wherein X, Y, and R, independently of one another, is each a H; halogen, wherein said halogen is selected from the group consisting of .sup.123 I, .sup.124 I, .sup.125 I, .sup.131 I, .sup.75 Br, .sup.76 Br, .sup.77 Br, .sup.82 Br, .sup.18 F, or .sup.210 At; small alkyl, small alkenyl, or small alkynyl, any of which contains from one to about six carbon atoms and optionally having a carbon atom replaced by an O or S; or halogen substituted-small alkyl, halogen substituted-small alkenyl, or halogen substituted-small alkynyl wherein said compound contains at least one radioacitve halogen. The compounds bind to the serotonin transporter. Depending upon the choice of halogen substituent, the compounds are useful for PET or SPECT imaging, diagnosis and treatment of psychiatric disorders such as depression, anxiety, obsessive-compulsive disorder, and other conditions associated with defects of serotonin transporter function.

The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo.

PubMed

Nguyen, Ho-Ngoc; Wey, Shiaw-Pyng; Juang, Jyuhn-Huarng; Sonaje, Kiran; Ho, Yi-Cheng; Chuang, Er-Yuan; Hsu, Chia-Wei; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

2011-04-01

Exendin-4 is a potent insulinotropic agent in diabetes patients; however, its therapeutic utility is limited due to the frequent injections required. In this study, an orally available exendin-4 formulation, using an enteric-coated capsule containing pH-responsive NPs, was developed. Following oral administration of (123)I-labeled-exendin-4 loaded NPs in rats, the biodistribution of the administered drug was investigated using a dual isotope dynamic SPECT/CT scanner. The results showed that the radioactivity of (123)I-exendin-4 propagated from the esophagus, stomach, and small intestine and then was absorbed into the systemic circulation; with time progressing, (123)I-exendin-4 was metabolized and excreted into the urinary bladder. In the in vivo dissolution study, it was found that the enteric-coated capsule remained intact while in the stomach; the capsule was completely dissolved in the proximal segment of the small intestine and the loaded contents were then released. Oral administration of the capsule containing exendin-4 loaded NPs showed a maximum plasma concentration at 5 h after treatment; the bioavailability, relative to its subcutaneous counterpart, was found to be 14.0 ± 1.8%. The absorbed exendin-4 could then stimulate the insulin secretion and provide a prolonged glucose-lowering effect. The aforementioned results suggest that the orally available exendin-4 formulation developed warrants further exploration as a potential therapy for diabetic patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

PubMed

Werner, Rudolf A; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G; Higuchi, Takahiro

2015-09-01

(18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-MIBG) was examined by PET and planar scintigraphy, respectively. Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, (18)F-LMI1195 and (123)I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

PubMed

Trott, C M; Ouyang, J; El Fakhri, G

2010-11-21

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

Five months' follow-up of patients with and without iodine-positive lymph node metastases of thyroid carcinoma as disclosed by (131)I-SPECT/CT at the first radioablation.

PubMed

Schmidt, Daniela; Linke, Rainer; Uder, Michael; Kuwert, Torsten

2010-04-01

In differentiated thyroid carcinoma (DTC), (131)I-SPECT/CT is more accurate in identifying radioiodine-positive lymph node metastases (LNM) than planar whole-body scans (WBS). The purpose of this study was to investigate the value of (131)I-SPECT/CT performed at the first radioablation to predict the occurrence and/or persistence of cervical radioiodine-positive LNM 5 months later. The study included 81 DTC patients that had had SPECT/ spiral CT after radioablation of thyroid remnants after thyroidectomy. The patients were re-examined 5 months later using (131)I-WBS performed at TSH stimulation. In addition, SPECT/CT of the neck was performed in patients with iodine-positive cervical foci to distinguish between thyroid remnant and LNM. The outcome variable of the study was the detection or exclusion of iodine-positive cervical LNM. Of 61 patients without a SPECT/CT diagnosis of (131)I-positive LNM at radioablation, 60 had no (131)I-positive LNM at follow-up. In the remaining patient of this group, a new radioiodine-positive LNM was detected. In 17 of 20 patients with a SPECT/CT diagnosis of (131)I-positive LNM (n = 19) or an indeterminate lesion (n = 1) at first radioablation, no (131)I-positive LNM were detected 5 months later. Radioiodine-positive LNM persisted in three patients of this group. (131)I-SPECT/CT has a high negative predictive value with regard to the occurrence of radioiodine-positive cervical LNM 5 months after initial therapy. The majority of iodine-positive LNM diagnosed by SPECT/CT at radioablation disappear within 5 months. These findings motivate further research into the value of (131)I-SPECT/CT of the neck for predicting recurrence and planning surgical reintervention in DTC.

The first 3':5'-cyclic nucleotide-amino acid complex: L-His-cIMP.

PubMed

Slepokura, Katarzyna

2012-08-01

In the crystal structure of the L-His-cIMP complex, i.e. L-histidinium inosine 3':5'-cyclic phosphate [systematic name: 5-(2-amino-2-carboxyethyl)-1H-imidazol-3-ium 7-hydroxy-2-oxo-6-(6-oxo-6,9-dihydro-1H-purin-9-yl)-4a,6,7,7a-tetrahydro-4H-1,3,5,2λ(5)-furo[3,2-d][1,3,2λ(5)]dioxaphosphinin-2-olate], C(6)H(10)N(3)O(2)(+)·C(10)H(10)N(4)O(7)P(-), the Hoogsteen edge of the hypoxanthine (Hyp) base of cIMP and the Hyp face are engaged in specific amino acid-nucleotide (His···cIMP) recognition, i.e. by abutting edge-to-edge and by π-π stacking, respectively. The Watson-Crick edge of Hyp and the cIMP phosphate group play a role in nonspecific His···cIMP contacts. The interactions between the cIMP anions (anti/C3'-endo/trans-gauche/chair conformers) are realized mainly between riboses and phosphate groups. The results for this L-His-cIMP complex, compared with those for the previously reported solvated L-His-IMP crystal structure, indicate a different nature of amino acid-nucleotide recognition and interactions upon the 3':5'-cyclization of the nucleotide phosphate group.

Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products.

PubMed

Zou, Liang; Sun, Lili; Zhang, Hui; Hui, Wenkai; Zou, Qiaogen; Zhu, Zheying

2017-07-01

The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products.

FMR1 Gene Expansion and Scans without Evidence of Dopaminergic Deficits in Parkinsonism Patients

PubMed Central

Hall, DA; Jennings, D; Seibyl, J; Tassone, F; Marek, K

2010-01-01

Purpose To determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients. Scope The authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41–60 CGG) with [123I] -CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density. Conclusions These results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than presynaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD). PMID:20702130

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

PubMed

Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-02-22

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance

PubMed Central

Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Bianco, Luciana Lo; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-01-01

Background Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Methods Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Results Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Conclusions Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway. PMID:20179754

Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance.

PubMed

A, Vijaya Bhaskar Reddy; Yusop, Zulkifli; Jaafar, Jafariah; Aris, Azmi B; Majid, Zaiton A; Umar, Khalid; Talib, Juhaizah

2016-09-05

In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm×2.1mm, 1.7μm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp-I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved iodine radiolabels for monoclonal antibody therapy.

PubMed

Stein, Rhona; Govindan, Serengulam V; Mattes, M Jules; Chen, Susan; Reed, Linda; Newsome, Guy; McBride, Bill J; Griffiths, Gary L; Hansen, Hans J; Goldenberg, David M

2003-01-01

A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs. We recently reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a residualizing iodine label that overcame many of the limitations that had impeded the development of residualizing iodine for clinical use. To determine the factors governing the therapeutic index of the labeled MAb, as well as the factors required for production of radioiodinated MAb in high yield and with high specific activity, variations in the peptide structure of IMP-R1 were evaluated. A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and charge were compared. Radioiodinations of the peptides followed by conjugations to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished radioimmunoconjugates in good overall incorporations, with immunoreactivities comparable to that of directly radioiodinated RS7. Specific activities of up to 8 mCi/mg and yields > 80% have been achieved. In vitro processing experiments showed marked increases in radioiodine retention with all of the adducts; radioiodine retention at 45 h was up to 86% greater in cells than with directly iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I-RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies in nude mice bearing human lung tumor xenografts. All of the residualizing substrates exhibited significantly enhanced retention in tumor in comparison to directly radioiodinated RS7, but the nontarget uptakes differed significantly among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention and low normal organ uptake, as well as superior radiochemical properties. The therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7 were equivalent, and both agents yielded significantly improved control of tumor growth compared with conventional (131)I-labeled RS7.

Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.

PubMed

Kiriyama, Tomonari; Kumita, Shin-Ichiro; Moroi, Masao; Nishimura, Tsunehiko; Tamaki, Nagara; Hasebe, Naoyuki; Kikuchi, Kenjiro

2015-01-01

The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled β-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.

A new era for Nuclear Medicine neuroimaging in Spain: Where do we start from in Spain?

PubMed

Balsa, M A; Camacho, V; Garrastachu, P; García-Solís, D; Gómez-Río, M; Rubí, S; Setoain, X; Arbizu, J

To determine the status of neuroimaging studies of Nuclear Medicine in Spain during 2013 and first quarter of 2014, in order to define the activities of the neuroimaging group of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM). A questionnaire of 14 questions was designed, divided into 3 parts: characteristics of the departments (equipment and professionals involved); type of scans and clinical indications; and evaluation methods. The questionnaire was sent to 166 Nuclear Medicine departments. A total of 54 departments distributed among all regions completed the questionnaire. Most departments performed between 300 and 800 neuroimaging examinations per year, representing more than 25 scans per month. The average pieces of equipment were three; half of the departments had a PET/CT scanner and SPECT/CT equipment. Scans performed more frequently were brain SPECT with 123 I-FP-CIT, followed by brain perfusion SPECT and PET with 18 F-FDG. The most frequent clinical indications were cognitive impairment followed by movement disorders. For evaluation of the images most sites used only visual assessment, and for the quantitative assessment the most used was quantification by region of interest. These results reflect the clinical activity of 2013 and first quarter of 2014. The main indications of the studies were cognitive impairment and movement disorders. Variability in the evaluation of the studies is among the challenges that will be faced in the coming years. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma.

PubMed

Bleeker, Gitta; Tytgat, Godelieve A M; Adam, Judit A; Caron, Huib N; Kremer, Leontien C M; Hooft, Lotty; van Dalen, Elvira C

2015-09-29

Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose ((18)F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. 1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. 2.1 To determine the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. This was performed within and between included studies. ¹²³I-MIBG (SPECT-CT) scintigraphy was the comparator test in this case. We searched the databases of MEDLINE/PubMed (1945 to 11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially relevant articles. Also we checked the reference lists of relevant articles and review articles, scanned conference proceedings and searched for unpublished studies by contacting researchers involved in this area. We included studies of a cross-sectional design or cases series of proven neuroblastoma, either retrospective or prospective, if they compared the results of ¹²³I-MIBG (SPECT-CT) scintigraphy or (18)F-FDG-PET(-CT) imaging, or both, with the reference standards or with each other. Studies had to be primary diagnostic and report on children aged between 0 to 18 years old with a neuroblastoma of any stage at first diagnosis or at recurrence. One review author performed the initial screening of identified references. Two review authors independently performed the study selection, extracted data and assessed the methodological quality.We used data from two-by-two tables, describing at least the number of patients with a true positive test and the number of patients with a false negative test, to calculate the sensitivity, and if possible, the specificity for each included study.If possible, we generated forest plots showing estimates of sensitivity and specificity together with 95% confidence intervals. Eleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of ¹²³I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of ¹²³I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies.One study reported on the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging (add-on test) in patients with negative ¹²³I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative ¹²³I-MIBG scan and a positive (18)F-FDG-PET(-CT) scan.The sensitivity of (18)F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to ¹²³I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of (18)F-FDG-PET(-CT) imaging was 100% versus 92% of ¹²³I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities. The reported sensitivities of ¹²³-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma.Only one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made.As described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate ¹²³I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be (18)F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed.The diagnostic accuracy of (18)F-FDG-PET(-CT) imaging in case of a negative ¹²³I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test ¹²³I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search.At the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term "the sensitivity to assess the presence of neuroblastoma" instead of "diagnostic accuracy" for the objectives.

D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

PubMed

Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

2011-02-14

Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

PubMed Central

Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

2015-01-01

Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan. PMID:26190980

Dynamic 3D analysis of myocardial sympathetic innervation: an experimental study using 123I-MIBG and a CZT camera.

PubMed

Giorgetti, Assuero; Burchielli, Silvia; Positano, Vincenzo; Kovalski, Gil; Quaranta, Angela; Genovesi, Dario; Tredici, Manuel; Duce, Valerio; Landini, Luigi; Trivella, Maria Giovanna; Marzullo, Paolo

2015-03-01

Data on the in vivo myocardial kinetics of (123)I-metaiodobenzylguanidine ((123)I-MIBG) are scarce and have always been obtained using planar acquisitions. To clarify the normal kinetics of (123)I-MIBG in vivo over time, we designed an experimental protocol using a 3-dimensional (3D) dynamic approach with a cadmium zinc telluride (CZT) camera. We studied 6 anesthetized pigs (mean body weight, 37 ± 4 kg). Left ventricular myocardial perfusion and sympathetic innervation were assessed using (99m)Tc-tetrofosmin (26 ± 6 MBq), (123)I-MIBG (54 ± 14 MBq), and a CZT camera. A normal perfusion/function match on gated SPECT was the inclusion criterion. A dynamic acquisition in list mode started simultaneously with the bolus injection of (123)I-MIBG, and data were collected every 5 min for the first 20 min and then at acquisition steps of 30, 60, 90, and 120 min. Each step was reconstructed using dedicate software and reframed (60 s/frame). On the reconstructed transaxial slice that best showed the left ventricular cavity, regions of interest were drawn to obtain myocardial and blood pool activities. Myocardial time-activity curves were generated by interpolating data between contiguous acquisition steps, corrected for radiotracer decay and injected dose, and fitted to a bicompartmental model. Time to myocardial maximum signal intensity (MSI), MSI value, radiotracer retention index (RI, myocardial activity/blood pool integral), and washout rate were calculated. The mediastinal signal was measured and fitted to a linear model. The myocardial MSI of (123)I-MIBG was reached within 5.57 ± 4.23 min (range, 2-12 min). The mean MSI was 0.426% ± 0.092%. Myocardial RI decreased over time and reached point zero at 176 ± 31 min (range, 140-229 min). The ratio between myocardial and mediastinal signal at 15 and 125 min and extrapolated at 176 and 4 h was 5.45% ± 0.61%, 4.33% ± 1.23% (not statistically significant vs. 15 min), 3.95% ± 1.46% (P < 0.03 vs. 125 min), and 3.63% ± 1.64% (P < 0.03 vs. 176 min), respectively. Mean global washout rate at 125 min was 15% ± 14% (range, 0%-34%), and extrapolated data at 176 min and 4 h were 18% ± 18% (range, 0.49%-45%) and 25% ± 23% (range, 1.7%-56.2%; not statistically significant vs. 176 min), respectively. 3D dynamic analysis of (123)I-MIBG suggests that myocardial peak uptake is reached more quickly than previously described. Myocardial RI decreases over time and, on average, is null about 3 h after injection. The combination of an early peak and variations in delayed myocardial uptake could result in a wide physiologic range of washout rates. Mediastinal activity appears to be constant over time and significantly lower than previously described in planar studies, resulting in a higher heart-to-mediastinum ratio. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Serotonin and dopamine transporter binding in children with autism determined by SPECT.

PubMed

Makkonen, Ismo; Riikonen, Raili; Kokki, Hannu; Airaksinen, Mauno M; Kuikka, Jyrki T

2008-08-01

Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8 y 8 mo [SD 3 y 10 mo]) with autism and 10 non-autistic comparison children (five males, five females; mean age 9 y 10 mo [SD 2 y 8 mo]) using single-photon emission computed tomography (SPECT) with [123 I] nor-beta-CIT. The children, with autism were studied during light sedation. They showed reduced serotonin transporter (SERT) binding capacity in the medial frontal cortex, midbrain, and temporal lobe areas. However, after correction due to the estimated effect of sedation, the difference remained significant only in the medial frontal cortex area (p=0.002). In the individuals with autism dopamine transporter (DAT) binding did not differ from that of the comparison group. The results indicate that SERT binding capacity is disturbed in autism. The reduction is more evident in adolescence than in earlier childhood. The low SERT binding reported here and the low serotonin synthesis capacity shown elsewhere may indicate maturation of a lesser number of serotonergic nerve terminals in individuals with autism.

Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database.

PubMed

Nakajima, Kenichi; Matsumoto, Naoya; Kasai, Tokuo; Matsuo, Shinro; Kiso, Keisuke; Okuda, Koichi

2016-04-01

As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of (123)I-MIBG sympathetic imaging was performed regarding heart-to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches.

The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp, F.F. Jr.; Ambrose, K.R.; Kropp, J.

1993-06-01

Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use ofmore » such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).« less

The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp, F.F. Jr.; Ambrose, K.R.; Kropp, J.

1993-01-01

Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use ofmore » such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).« less

Elucidating the Role of Residue 67 in IMP-Type Metallo-β-Lactamase Evolution.

PubMed

LaCuran, Alecander E; Pegg, Kevin M; Liu, Eleanor M; Bethel, Christopher R; Ai, Ni; Welsh, William J; Bonomo, Robert A; Oelschlaeger, Peter

2015-12-01

Antibiotic resistance in bacteria is ever changing and adapting, as once-novel β-lactam antibiotics are losing their efficacy, primarily due to the production of β-lactamases. Metallo-β-lactamases (MBLs) efficiently inactivate a broad range of β-lactam antibiotics, including carbapenems, and are often coexpressed with other antibacterial resistance factors. The rapid dissemination of MBLs and lack of novel antibacterials pose an imminent threat to global health. In an effort to better counter these resistance-conferring β-lactamases, an investigation of their natural evolution and resulting substrate specificity was employed. In this study, we elucidated the effects of different amino acid substitutions at position 67 in IMP-type MBLs on the ability to hydrolyze and confer resistance to a range of β-lactam antibiotics. Wild-type β-lactamases IMP-1 and IMP-10 and mutants IMP-1-V67A and IMP-1-V67I were characterized biophysically and biochemically, and MICs for Escherichia coli cells expressing these enzymes were determined. We found that all variants exhibited catalytic efficiencies (kcat/Km) equal to or higher than that of IMP-1 against all tested β-lactams except penicillins, against which IMP-1 and IMP-1-V67I showed the highest kcat/Km values. The substrate-specific effects of the different amino acid substitutions at position 67 are discussed in light of their side chain structures and possible interactions with the substrates. Docking calculations were employed to investigate interactions between different side chains and an inhibitor used as a β-lactam surrogate. The differences in binding affinities determined experimentally and computationally seem to be governed by hydrophobic interactions between residue 67 and the inhibitor and, by inference, the β-lactam substrates. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

FMR1 gene expansion and scans without evidence of dopaminergic deficits in parkinsonism patients.

PubMed

Hall, D A; Jennings, D; Seibyl, J; Tassone, F; Marek, K

2010-11-01

To determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients. The authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41-60 CGG) with [(123)I]β-CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density. These results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than pre-synaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD). Copyright © 2010 Elsevier Ltd. All rights reserved.

Task-based design of a synthetic-collimator SPECT system used for small animal imaging.

PubMed

Lin, Alexander; Kupinski, Matthew A; Peterson, Todd E; Shokouhi, Sepideh; Johnson, Lindsay C

2018-05-07

In traditional multipinhole SPECT systems, image multiplexing - the overlapping of pinhole projection images - may occur on the detector, which can inhibit quality image reconstructions due to photon-origin uncertainty. One proposed system to mitigate the effects of multiplexing is the synthetic-collimator SPECT system. In this system, two detectors, a silicon detector and a germanium detector, are placed at different distances behind the multipinhole aperture, allowing for image detection to occur at different magnifications and photon energies, resulting in higher overall sensitivity while maintaining high resolution. The unwanted effects of multiplexing are reduced by utilizing the additional data collected from the front silicon detector. However, determining optimal system configurations for a given imaging task requires efficient parsing of the complex parameter space, to understand how pinhole spacings and the two detector distances influence system performance. In our simulation studies, we use the ensemble mean-squared error of the Wiener estimator (EMSE W ) as the figure of merit to determine optimum system parameters for the task of estimating the uptake of an 123 I-labeled radiotracer in three different regions of a computer-generated mouse brain phantom. The segmented phantom map is constructed by using data from the MRM NeAt database and allows for the reduction in dimensionality of the system matrix which improves the computational efficiency of scanning the system's parameter space. To contextualize our results, the Wiener estimator is also compared against a region of interest estimator using maximum-likelihood reconstructed data. Our results show that the synthetic-collimator SPECT system outperforms traditional multipinhole SPECT systems in this estimation task. We also find that image multiplexing plays an important role in the system design of the synthetic-collimator SPECT system, with optimal germanium detector distances occurring at maxima in the derivative of the percent multiplexing function. Furthermore, we report that improved task performance can be achieved by using an adaptive system design in which the germanium detector distance may vary with projection angle. Finally, in our comparative study, we find that the Wiener estimator outperforms the conventional region of interest estimator. Our work demonstrates how this optimization method has the potential to quickly and efficiently explore vast parameter spaces, providing insight into the behavior of competing factors, which are otherwise very difficult to calculate and study using other existing means. © 2018 American Association of Physicists in Medicine.

Performance of a high-sensitivity dedicated cardiac SPECT scanner for striatal uptake quantification in the brain based on analysis of projection data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Mi-Ae; Moore, Stephen C.; McQuaid, Sarah J.

Purpose: The authors have previously reported the advantages of high-sensitivity single-photon emission computed tomography (SPECT) systems for imaging structures located deep inside the brain. DaTscan (Isoflupane I-123) is a dopamine transporter (DaT) imaging agent that has shown potential for early detection of Parkinson disease (PD), as well as for monitoring progression of the disease. Realizing the full potential of DaTscan requires efficient estimation of striatal uptake from SPECT images. They have evaluated two SPECT systems, a conventional dual-head gamma camera with low-energy high-resolution collimators (conventional) and a dedicated high-sensitivity multidetector cardiac imaging system (dedicated) for imaging tasks related to PD.more » Methods: Cramer-Rao bounds (CRB) on precision of estimates of striatal and background activity concentrations were calculated from high-count, separate acquisitions of the compartments (right striata, left striata, background) of a striatal phantom. CRB on striatal and background activity concentration were calculated from essentially noise-free projection datasets, synthesized by scaling and summing the compartment projection datasets, for a range of total detected counts. They also calculated variances of estimates of specific-to-nonspecific binding ratios (BR) and asymmetry indices from these values using propagation of error analysis, as well as the precision of measuring changes in BR on the order of the average annual decline in early PD. Results: Under typical clinical conditions, the conventional camera detected 2 M counts while the dedicated camera detected 12 M counts. Assuming a normal BR of 5, the standard deviation of BR estimates was 0.042 and 0.021 for the conventional and dedicated system, respectively. For an 8% decrease to BR = 4.6, the signal-to-noise ratio were 6.8 (conventional) and 13.3 (dedicated); for a 5% decrease, they were 4.2 (conventional) and 8.3 (dedicated). Conclusions: This implies that PD can be detected earlier with the dedicated system than with the conventional system; therefore, earlier identification of PD progression should be possible with the high-sensitivity dedicated SPECT camera.« less

Accuracy of partial volume effect correction in clinical molecular imaging of dopamine transporter using SPECT

NASA Astrophysics Data System (ADS)

Soret, Marine; Alaoui, Jawad; Koulibaly, Pierre M.; Darcourt, Jacques; Buvat, Irène

2007-02-01

ObjectivesPartial volume effect (PVE) is a major source of bias in brain SPECT imaging of dopamine transporter. Various PVE corrections (PVC) making use of anatomical data have been developed and yield encouraging results. However, their accuracy in clinical data is difficult to demonstrate because the gold standard (GS) is usually unknown. The objective of this study was to assess the accuracy of PVC. MethodTwenty-three patients underwent MRI and 123I-FP-CIT SPECT. The binding potential (BP) values were measured in the striata segmented on the MR images after coregistration to SPECT images. These values were calculated without and with an original PVC. In addition, for each patient, a Monte Carlo simulation of the SPECT scan was performed. For these simulations where true simulated BP values were known, percent biases in BP estimates were calculated. For the real data, an evaluation method that simultaneously estimates the GS and a quadratic relationship between the observed and the GS values was used. It yields a surrogate mean square error (sMSE) between the estimated values and the estimated GS values. ResultsThe averaged percent difference between BP measured for real and for simulated patients was 0.7±9.7% without PVC and was -8.5±14.5% with PVC, suggesting that the simulated data reproduced the real data well enough. For the simulated patients, BP was underestimated by 66.6±9.3% on average without PVC and overestimated by 11.3±9.5% with PVC, demonstrating the greatest accuracy of BP estimates with PVC. For the simulated data, sMSE were 27.3 without PVC and 0.90 with PVC, confirming that our sMSE index properly captured the greatest accuracy of BP estimates with PVC. For the real patient data, sMSE was 50.8 without PVC and 3.5 with PVC. These results were consistent with those obtained on the simulated data, suggesting that for clinical data, and despite probable segmentation and registration errors, BP were more accurately estimated with PVC than without. ConclusionPVC was very efficient to greatly reduce the error in BP estimates in clinical imaging of dopamine transporter.

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

PubMed

Pouw, Bas; de Wit-van der Veen, Linda J; van Duijnhoven, Frederieke; Rutgers, Emiel J Th; Stokkel, Marcel P M; Valdés Olmos, Renato A; Vrancken Peeters, Marie-Jeanne T F D

2016-05-01

Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery. Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds. Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous. Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

Interface Message Processors for the ARPA Computer Network

DTIC Science & Technology

1975-04-01

Pluribus IMP construction and checkout; sizeable changes to the i*4P message-processing algorithms: and Satellite IMP issues. The IMP message...extremely low cost modification design. We have begun to consider changes to the MLC design which would enable the MLC to suppress continuous breaks...existing authentication mechanisms need not make these changes . 2.7 Other Topics During the first quarter BBN constructed an environmental test chamber

[Relationship between the regional cerebral blood flow and the cognitive function and anosmia in patients with Parkinson disease and Alzheimer disease].

PubMed

Imamura, Kazuhiro; Matumoto, Shinjirou; Mabuchi, Naoki; Kobayashi, Yasushi; Okayasu, Naoki; Watanabe, Kenichi

2009-06-01

We compared the relationship between regional cerebral blood flow (rCBF) of the olfactory area and the cognitive function and anosmia in patient with Parkinson disease (PD) and in those with Alzheimer disease (AD). UPDRS III, MMSE, HDS-R, CDR, Beck Depression Inventory (BDI) were employed in this study. The subjects included 56 PD patients (average age 71.4+/-9.69 years), 23 AD patients (average age 73.3+/-7.12 years), 12 patients with mild cognitive impairment (MCI) (average age 72.5+/-6.89 years), and 9 age-matched controls (NC) (average age 73.8+/-6.61 years). Next we intravenously injected 1 ampule of thiamine propyldisulphide (Alinamin) and confirmed anosmia. In addition, we performed 123I-IMP SPECT (SEE methods) and satistically determined rCBF of the olfactory area based on the basis of the Z scores of the interest area. Anosima was detected in approximately 40% of the PD and AD patients. The HDS-R and MMSE scores were significantly higher in patients with anosima than in those without anosima; the CDR scores were significantly higher in the former than in the latter. Further, the incidence of anosima in PD patients and AD patients with MCI increased with an increase in the CDR scores. In order to determine the rCBF of the olfactory area of the PD and AD patients. As to rCBF of the olfactory area, we examined left and right Z scores of hippocampus, parahippocampus, amygdala, and uncus at Talairach level 3 and the scores of the Brodmann area 28, 34, 35, and 36 at Talairach level 5. In patients with anosmia, the Z scores were significantly high in cases with anosmia in all areas except the right Brodmann area 34 in PD patients and the right Brodmann area 28 and bilateral the Brodmann area 34 of both sides in AD patients. Some parts of the olfactory area are closely related to cognitive function, and it appeares that a reduced rCBF in the olfactory areas may lead to a functional decline in these regions which may cause anosmia and cognitive decline in PD and AD patients.

Dissemination of IMP-6 metallo-β-lactamase-producing Pseudomonas aeruginosa sequence type 235 in Korea.

PubMed

Seok, Yoonmi; Bae, Il Kwon; Jeong, Seok Hoon; Kim, Soo Hyun; Lee, Hyukmin; Lee, Kyungwon

2011-12-01

To investigate the epidemiological traits of Pseudomonas aeruginosa clinical isolates producing metallo-β-lactamases (MBLs) in Korea. A total of 386 non-duplicate P. aeruginosa clinical isolates were collected from Korea in 2009. Detection of MBL genes was performed by PCR. The genetic organization of class 1 integrons carrying the MBL gene cassette was investigated by PCR mapping and sequencing. The epidemiological relationships of the isolates were investigated by multilocus sequence typing and PFGE. Of 386 P. aeruginosa isolates, 30 (7.8%) isolates carried the bla(IMP-6) gene and 1 (0.3%) isolate carried the bla(VIM-2) gene. A probe specific for the bla(IMP-6) gene was hybridized to an ∼950 kbp I-CeuI-macrorestriction fragment from all 30 isolates and a probe specific for the bla(VIM-2) gene also hybridized to an ∼500 kbp I-CeuI-macrorestriction fragment from 1 isolate (BDC10). All 31 MBL-producing isolates shared an identical sequence type (ST), ST235, and they carried the same bla(OXA-50) allelic type, bla(OXA-50g). All MBL-producing isolates showed similar XbaI-macrorestriction patterns (similarity >85%), irrespective of MBL genotype. P. aeruginosa ST235 carrying the chromosomally located bla(IMP-6) gene is widely disseminated in Korea.

Description of IMP-31, a novel metallo-β-lactamase found in an ST235 Pseudomonas aeruginosa strain in Western Germany.

PubMed

Pfennigwerth, Niels; Geis, Gabriele; Gatermann, Sören G; Kaase, Martin

2015-07-01

The objective of this study was to characterize a novel IMP-type metallo-β-lactamase (MBL) found in an MDR clinical isolate of Pseudomonas aeruginosa. The P. aeruginosa isolate NRZ-00156 was recovered from an inguinal swab from a patient hospitalized in Western Germany and showed high MICs of carbapenems. MBL production was analysed by Etest for MBLs, an EDTA combined disc test and an EDTA bioassay. Typing of the isolate was performed by MLST. Genetic characterization of the new blaIMP gene was performed by sequencing the PCR products. A phylogenetic tree was constructed. The novel blaIMP gene was expressed in Escherichia coli TOP10 and the enzyme was subjected to biochemical characterization. The P. aeruginosa isolate NRZ-00156 expressed the ST235 allelic profile and was resistant to all the β-lactams tested except aztreonam. The isolate was positive for MBL production and harboured a new IMP allele, blaIMP-31, located on a disrupted class I integron [also carrying the blaOXA-35, aac(6')-Ib, aac(3)-Ic and aphA15 genes]. Its closest relative was IMP-35, with 96.7% amino acid identity. Expression of blaIMP-31 demonstrated that E. coli TOP10 producing IMP-31 had elevated resistance to all the β-lactams tested except aztreonam. Kinetic data were obtained for both IMP-31 and IMP-1. In comparison with IMP-1, IMP-31 showed weaker hydrolytic activity against all the β-lactams tested, which resulted from lower kcat values. The characterization of the new IMP-type gene blaIMP-31 from an ST235 P. aeruginosa isolate indicates an ongoing spread of highly divergent IMP-type carbapenemases in clinical P. aeruginosa strains and highlights the continuous need for the prevention of nosocomial infections caused by MDR Gram-negative bacteria. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

IMP-I spacecraft final magnetic tests

NASA Technical Reports Server (NTRS)

Harris, C. A.

1972-01-01

The increased IMP-I spacecraft spin axis moment resulting from excessive field exposures during environmental testing substantiated the need for a final pre-launch magnetic deperm and measurement. By performing a dc rotation deperm it was possible to reduce this moment below the previous initial test post deperm magnitude. In addition, the magnetic field disturbance at the flight magnetometer diminished to below 0.1 nanotesla (gamma) in all directions.

Time course evaluation of myocardial perfusion after reperfusion therapy by 99mTc-tetrofosmin SPECT in patients with acute myocardial infarction.

PubMed

Tanaka, R; Nakamura, T

2001-09-01

Myocardial perfusion imaging with 99mTc-labeled agents immediately after reperfusion therapy can underestimate myocardial salvage. It is also conceivable that delayed imaging is useful for assessing the risk area. However, to our knowledge, very few studies have sequentially evaluated these image changes. We conducted 99mTc-tetrofosmin (TF) and 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) SPECT before and after reperfusion to treat acute myocardial infarction and quantified changes in TF myocardial accumulation and reverse redistribution. Seventeen patients with a first myocardial infarction underwent successful reperfusion. We examined SPECT images obtained at the onset (preimage), those acquired 30 min (early image) and 6 h (delayed image) after TF injection, and images acquired 1, 4, 7, and 20 d after reperfusion (post-1-d, post-4-d, post-7-d, and post-20-d image, respectively). We also examined BMIPP SPECT images after 7 +/- 1.8 d (BMIPP image). Polar maps were divided into 48 segments to calculate percentage uptake, and time course changes in segment numbers below 60% were observed as abnormal area. Moreover, cardiac function was analyzed by gated TF SPECT on 1 and 20 d after reperfusion. In reference to the abnormal area on the early images, the post-1-d image was significantly improved compared with the preimage (P < 0.01) as was the post-7-d image compared with the post-1-d and post-4-d images (P < 0.05, respectively). However, post-20-d and post-7-d images did not significantly differ. Therefore, the improvement in myocardial accumulation reached a plateau 7 d after reperfusion. On the other hand, the abnormal area on the delayed images was significantly greater (P < 0.01) compared with that on the early images from 4 to 20 d after reperfusion, as the value was essentially constant. The correlations of the abnormal area between the preimage and the post-7-d delayed image, the preimage and the BMIPP image, and the post-7-d delayed image and the BMIPP image were very close (r = 0.963, r = 0.981, and r = 0.975, respectively). Gated TF SPECT revealed that the left ventricular ejection fraction was not significantly different (P = not significant) between 1 and 20 d after reperfusion, but regional wall motion was significantly different after reperfusion (P < 0.05). These results suggest that the interval between reperfusion therapy and TF SPECT should be 7 d to evaluate the salvage effect and that TF delayed and BMIPP images are both useful in estimation of risk area.

Subacute cardiac rubidium-82 positron emission tomography (82Rb-PET) to assess myocardial area at risk, final infarct size, and myocardial salvage after STEMI.

PubMed

Ghotbi, Adam Ali; Kjaer, Andreas; Nepper-Christensen, Lars; Ahtarovski, Kiril Aleksov; Lønborg, Jacob Thomsen; Vejlstrup, Niels; Kyhl, Kasper; Christensen, Thomas Emil; Engstrøm, Thomas; Kelbæk, Henning; Holmvang, Lene; Bang, Lia E; Ripa, Rasmus Sejersten; Hasbak, Philip

2018-06-01

Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82 Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR). Twelve STEMI patients were injected with 99m Tc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82 Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index. SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78). 82 Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population.

Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism.

PubMed

Kim, Jong-Min; Hong, Susie; Kim, Gyoung Pyoung; Choi, Yoon Jae; Kim, Yu Kyeong; Park, Sung Sup; Kim, Sang Eun; Jeon, Beom S

2007-10-01

To examine the presence of an ATXN2 mutation in patients with parkinsonism in the Korean population and to find the difference in the ATXN2 mutation between ataxic and parkinsonian phenotypes. Survey. Seoul National University Hospital (a referral center). Patients Patients with Parkinson disease (PD) (n = 468) and the Parkinson variant of multiple system atrophy (MSA-P) (n = 135) who were seen at our Department of Neurology during the past 3 years. CAG expansion in spinocerebellar ataxia type 2 (SCA2) alleles was assessed by polymerase chain reaction amplification and fragment analysis, and its size and interruption were verified by cloning and sequencing. SCA2 was tested also in the family members of the probands. Striatal dopamine transporter (DAT) and D(2) receptor status were evaluated in the probands and their SCA2-positive family members using iodine I 123 [(123)I]-radiolabeled fluoropropyl (FP) 2-carbomethoxy-3-(4-iodophenyl) tropane (CIT) with single-photon emission computed tomography (SPECT) and carbon C 11 [(11)C]-radiolabeled raclopride positron emission tomography (PET). We found 3 patients with apparently sporadic disease with expanded CAG repeats in the ATXN2 locus. Two patients had a PD phenotype. The third patient showed an MSA-P phenotype. The CAG repeats in the ATXN2 locus of the patients were 35/22, 34/22, and 32/22, respectively (range in normal population, 19-27). The size of repeats was lower than the CAG repeats (38-51) in ataxic SCA2 in our population. The sequence of expanded CAG repeats was interrupted by CAA as (CAG)(n)(CAA)(CAG)(8) in all the patients. DNA analyses in 2 families showed 2 asymptomatic carriers in each family. In the patient with the PD phenotype, striatal DAT loss was more severe in the putamen than the caudate, and [(11)C]raclopride PET showed an increased relative putamen-caudate binding ratio. The patient with the MSA-P phenotype had severe DAT loss throughout the striatum. Two of 3 asymptomatic carriers had striatal DAT loss. This study demonstrates that SCA2 is one of the genetic causes of PD and MSA-P. All 3 patients had apparently sporadic disease, emphasizing the need to screen even in patients with nonfamilial disease. CAG repeats were in the low expansion range and interrupted by CAA in all patients in the low-range expansion. Therefore, accurate determination of CAG expansion and ATXN2 sequencing are warranted. [(123)I]FP-CIT SPECT and [(11)C]raclopride PET provide a useful way to evaluate the degree of nigrostriatal dopaminergic damage in SCA2-related parkinsonism and gene carriers.

1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

PubMed Central

Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

2008-01-01

Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users.

PubMed

de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; den Heeten, Gerard J; van den Brink, Wim

2008-11-01

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.

Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes

PubMed Central

Shin, Dong Hoon; Bang, Oh Young; Joo, In Soo; Huh, Kyoon

2006-01-01

Background and Purpose 123I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes. Methods Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study. Results Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34±0.15 vs 1.79±0.19; delayed, 1.29±0.15 vs 2.06±0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68±0.23; delayed, 1.80±0.34, p<0.001), DIP (early, 1.83±0.24; delayed, 2.07±0.4, p<0.001), or CBD (early, 1.85±0.01; delayed, 1.99±0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD. Conclusions This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes. PMID:20396485

Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis.

PubMed

Egerton, A; Modinos, G; Ferrera, D; McGuire, P

2017-06-06

Data from animal models and from postmortem studies suggest that schizophrenia is associated with brain GABAergic dysfunction. The extent to which this is reflected in data from in vivo studies of GABA function in schizophrenia is unclear. The Medline database was searched to identify articles published until 21 October 2016. The search terms included GABA, proton magnetic resonance spectroscopy ( 1 H-MRS), positron emission tomography (PET), single photon emission computed tomography (SPECT), schizophrenia and psychosis. Sixteen GABA 1 H-MRS studies (538 controls, 526 patients) and seven PET/SPECT studies of GABA A /benzodiazepine receptor (GABA A /BZR) availability (118 controls, 113 patients) were identified. Meta-analyses of 1 H-MRS GABA in the medial prefrontal cortex (mPFC), parietal/occipital cortex (POC) and striatum did not show significant group differences (mFC: g=-0.3, 409 patients, 495 controls, 95% confidence interval (CI): -0.6 to 0.1; POC: g=-0.3, 139 patients, 111 controls, 95% CI: -0.9 to 0.3; striatum: g=-0.004, 123 patients, 95 controls, 95% CI: -0.7 to 0.7). Heterogeneity across studies was high (I 2 >50%), and this was not explained by subsequent moderator or meta-regression analyses. There were insufficient PET/SPECT receptor availability studies for meta-analyses, but a systematic review did not suggest replicable group differences in regional GABA A /BZR availability. The current literature does not reveal consistent alterations in in vivo GABA neuroimaging measures in schizophrenia, as might be hypothesized from animal models and postmortem data. The analysis highlights the need for further GABA neuroimaging studies with improved methodology and addressing potential sources of heterogeneity.

Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis

PubMed Central

Egerton, A; Modinos, G; Ferrera, D; McGuire, P

2017-01-01

Data from animal models and from postmortem studies suggest that schizophrenia is associated with brain GABAergic dysfunction. The extent to which this is reflected in data from in vivo studies of GABA function in schizophrenia is unclear. The Medline database was searched to identify articles published until 21 October 2016. The search terms included GABA, proton magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), single photon emission computed tomography (SPECT), schizophrenia and psychosis. Sixteen GABA 1H-MRS studies (538 controls, 526 patients) and seven PET/SPECT studies of GABAA/benzodiazepine receptor (GABAA/BZR) availability (118 controls, 113 patients) were identified. Meta-analyses of 1H-MRS GABA in the medial prefrontal cortex (mPFC), parietal/occipital cortex (POC) and striatum did not show significant group differences (mFC: g=−0.3, 409 patients, 495 controls, 95% confidence interval (CI): −0.6 to 0.1; POC: g=−0.3, 139 patients, 111 controls, 95% CI: −0.9 to 0.3; striatum: g=−0.004, 123 patients, 95 controls, 95% CI: −0.7 to 0.7). Heterogeneity across studies was high (I2>50%), and this was not explained by subsequent moderator or meta-regression analyses. There were insufficient PET/SPECT receptor availability studies for meta-analyses, but a systematic review did not suggest replicable group differences in regional GABAA/BZR availability. The current literature does not reveal consistent alterations in in vivo GABA neuroimaging measures in schizophrenia, as might be hypothesized from animal models and postmortem data. The analysis highlights the need for further GABA neuroimaging studies with improved methodology and addressing potential sources of heterogeneity. PMID:28585933

Effects of exogenous inosine monophosphate on growth performance, flavor compounds, enzyme activity, and gene expression of muscle tissues in chicken.

PubMed

Yan, Junshu; Liu, Peifeng; Xu, Liangmei; Huan, Hailin; Zhou, Weiren; Xu, Xiaoming; Shi, Zhendan

2018-04-01

The goal of this experiment was to examine effects of diets supplemented with exogenous inosine monophosphate (IMP) on the growth performance, flavor compounds, enzyme activity and gene expression of chicken. A total of 1,500 healthy, 1-day-old male 3-yellow chickens were used for a 52-d experimental period. Individuals were randomly divided into 5 groups (group I, II, III, IV, V) with 6 replicates per group, and fed a basal diet supplemented with 0.0, 0.05, 0.1, 0.2, and 0.3% IMP, respectively. There was no significant response to the increasing dietary IMP level in average daily feed intake (ADFI), average daily gain (ADG), and feed:gain ratio (F/G) (P ≥ 0.05). IMP content of the breast and thigh muscle showed an exponential and linear response to the increasing dietary IMP level (P < 0.05), the highest IMP content was obtained when the diet with 0.3% and 0.2% exogenous IMP was fed. There were significant effects of IMP level in diet on free amino acids (FAA) (exponential, linear and quadratic effect, P < 0.05) and delicious amino acids (DAA) (quadratic effect, P < 0.01) content in breast muscle. FAA and DAA content in thigh muscle showed an exponential and linear response (P < 0.05), and quadratic response (P < 0.01) to the increasing dietary IMP level, the highest FAA and DAA content was obtained when the diet with 0.2% exogenous IMP was fed. Dietary IMP supplementation had a quadratic effect on 5΄-NT and the alkaline phosphatase (ALP) enzyme activity in the breast muscle (P < 0.05), and the adenosine triphosphate (ATP) enzyme activity in the thigh muscles increased exponentially and linearly with increasing IMP level in diet (exponential effect, P = 0.061; linear effect, P = 0.059). Cyclohydrolase (ATIC) gene expression in thigh muscle had a quadratic response to the increasing dietary IMP level (P < 0.05), 0.2% exogenous IMP group had the highest (AMPD1) gene expression of the breast muscle and ATIC gene expression of the thigh muscle. These results indicate that dietary IMP did not affect the growth performance of chicken, the diet with 0.2 to 0.3% exogenous IMP is optimal to improve the meat flavor quality in chicken.

Antenna Gain Loss and Pattern Degradation due to Transmission Through Dielectric Radomes

DTIC Science & Technology

1993-03-01

INP IF(ABS(ZH(I)).LT..001) ZH(I)=0. IF(ABS(RH(I)).LT..O01) RH(I)=O. ZHB=ZH(I)/BK RHB =RH(I)/BK C ASSIGN SURFACE IMPEDANCE AT THIS POINT. THE SURFACE...IMPEDANCE OF SEGMENT C I IS ZLO(I) IF(ICALC.EQ.O) ZlO(I)=IMP/(120.*PI) IF(ISEG.EQ.0) WRITE(8,8004) IZHB, RHB ,IMP 52 CONTINUE 8004 FORMAT(IIX,I4,4X,F8.3,8X...ROBS*COS (TEX) CALL CIRCRTP(CNPHI,XP,AP,ARAD,THSPHS, * - PHR, RHB ,ZHB,CIRCR,,CIRCT,CIRCP) C REMOVE THE h/R DEPENDENCE BECAUSE EXP(-jkR)/R IS OMITTED IN C

Dopamine efflux in response to ultraviolet radiation in addicted sunbed users

PubMed Central

Aubert, Pamela M.; Seibyl, John P.; Price, Julianne L.; Harris, Thomas S.; Filbey, Francesca M.; Jacobe, Heidi; Devous, Michael D.; Adinoff, Bryon

2017-01-01

Compulsive tanning despite awareness of ultraviolet radiation (UVR) carcinogenicity may represent an “addictive” behavior. Many addictive disorders are associated with alterations in dopamine (D2/D3) receptor binding and dopamine reactivity in the brain’s reward pathway. To determine if compulsive tanners exhibited neurobiologic responses similar to other addictive disorders, this study assessed basal striatal D2/D3 binding and UVR-induced striatal dopamine efflux in ten addicted and ten infrequent tanners. In a double-blind crossover trial, UVR or sham UVR was administered in separate sessions during brain imaging with single photon emission computerized tomography (SPECT). Basal D2/D3 receptor density and UVR-induced dopamine efflux in the caudate were assessed using 123I-iodobenzamide (123I-IBZM) binding potential non-displaceable (BPnd). Basal BPnd did not significantly differ between addicted and infrequent tanners. Whereas neither UVR nor sham UVR induced significant changes in bilateral caudate BPnd in either group, post-hoc analyses revealed left caudate BPnd significantly decreased (reflecting increased dopamine efflux) in the addicted tanners – but not the infrequent tanners –during the UVR session only. Bilateral ΔBPnd correlated with tanning severity only in the addicted tanners. These preliminary findings are consistent with a stronger neural rewarding response to UVR in addicted tanners, supporting a cutaneous-neural connection driving excessive sunbed use. PMID:27085608

Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method.

PubMed

Kumar, Ajay; Devineni, Subba Rao; Dubey, Shailender Kumar; Kumar, Pradeep; Srivastava, Vishal; Ambulgekar, Girish; Jain, Mohit; Gupta, Dharmendra Kumar; Singh, Gurmeet; Kumar, Rajesh; Hiriyanna, S G; Kumar, Pramod

2016-10-17

Four impurities (Imp-I-IV) were detected using gradient HPLC method in few laboratory batches of acrivastine in the level of 0.03-0.12% and three impurities (Imp-I-III) were found to be known and one (Imp-IV) was unknown. In forced degradation study, the drug is degraded into four degradation products under oxidation and photolytic conditions. Two impurities (Imp-III and -IV) were concurred with process related impurities whereas Imp-V and -VI were identified as new degradation impurities. Based on LC-ESI/MS n study, the chemical structures of new impurities were presumed as 1-[(2E)-3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}prop-2-en-1-yl]pyrrolidin-1-ium-1-olate (Imp-IV), 1-{[3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}oxiran-2-yl]methyl}pyrrolidin-1-ium-1-olate (Imp-V) and 2-[2-(4-methylphenyl)-3-[(1-oxidopyrrolidin-1-ium-1-yl)methyl]oxiran-2-yl]-6-[(1E)-3-oxobut-1-en-1-yl]pyridin-1-ium-1-olate (Imp-VI), and confirmed by their synthesis followed by spectroscopic analysis, IR, NMR ( 1 H, 13 C) and mass. An efficient and selective high-performance liquid chromatography method has been developed and resolved well the drug related substances on a Phenomenex Gemini C-18 (250×4.6mm, particle size 5μm) column. The mobile phase was composed of sodium dihydrogen phosphate (10mM) and methanol, temperature at 25°C, and a PDA detector set at 254nm used for detection. The method was validated with respect to specificity, linearity, precision, accuracy, and sensitivity and satisfactory results were achieved. Identification, synthesis, characterization of impurities and method validation were first reported in this paper. Copyright © 2016 Elsevier B.V. All rights reserved.

Circular Probable Error for Circular and Noncircular Gaussian Impacts

DTIC Science & Technology

2012-09-01

1M simulated impacts ph(k)=mean(imp(:,1).^2+imp(:,2).^2<=CEP^2); % hit frequency on CEP end phit (j)=mean(ph...avg 100 hit frequencies to “incr n” end % GRAPHICS plot(i, phit ,’r-’); % error exponent versus Ph estimate

Intramuscular Pressure of Tibialis Anterior Reflects Ankle Torque but Does Not Follow Joint Angle-Torque Relationship.

PubMed

Ateş, Filiz; Davies, Brenda L; Chopra, Swati; Coleman-Wood, Krista; Litchy, William J; Kaufman, Kenton R

2018-01-01

Intramuscular pressure (IMP) is the hydrostatic fluid pressure that is directly related to muscle force production. Electromechanical delay (EMD) provides a link between mechanical and electrophysiological quantities and IMP has potential to detect local electromechanical changes. The goal of this study was to assess the relationship of IMP with the mechanical and electrical characteristics of the tibialis anterior muscle (TA) activity at different ankle positions. We hypothesized that (1) the TA IMP and the surface EMG (sEMG) and fine-wire EMG (fwEMG) correlate to ankle joint torque, (2) the isometric force of TA increases at increased muscle lengths, which were imposed by a change in ankle angle and IMP follows the length-tension relationship characteristics, and (3) the electromechanical delay (EMD) is greater than the EMD of IMP during isometric contractions. Fourteen healthy adults [7 female; mean ( SD ) age = 26.9 (4.2) years old with 25.9 (5.5) kg/m 2 body mass index] performed (i) three isometric dorsiflexion (DF) maximum voluntary contraction (MVC) and (ii) three isometric DF ramp contractions from 0 to 80% MVC at rate of 15% MVC/second at DF, Neutral, and plantarflexion (PF) positions. Ankle torque, IMP, TA fwEMG, and TA sEMG were measured simultaneously. The IMP, fwEMG, and sEMG were significantly correlated to the ankle torque during ramp contractions at each ankle position tested. This suggests that IMP captures in vivo mechanical properties of active muscles. The ankle torque changed significantly at different ankle positions however, the IMP did not reflect the change. This is explained with the opposing effects of higher compartmental pressure at DF in contrast to the increased force at PF position. Additionally, the onset of IMP activity is found to be significantly earlier than the onset of force which indicates that IMP can be designed to detect muscular changes in the course of neuromuscular diseases impairing electromechanical transmission.

Nicotinic α4β2 acetylcholine receptors and cognitive function in Parkinson's disease.

PubMed

Lorenz, R; Samnick, S; Dillmann, U; Schiller, M; Ong, M F; Faßbender, K; Buck, A; Spiegel, J

2014-09-01

Idiopathic Parkinson's disease (IPD) is characterized by the clinical motor symptoms of hypokinesia, rigidity, and tremor. Apart from these motor symptoms, cognitive deficits often occur in IPD. The positive effect of cholinesterase inhibitors on cognitive deficits in IPD and findings of earlier molecular imaging studies suggest that the cholinergic system plays an important role in the origin of cognitive decline in IPD. Twenty-five non-demented patients with IPD underwent a 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) SPECT to visualize α4β2 nicotinic acetylcholine receptors (nAchR) and cognitive testing with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery to identify domains of cognitive dysfunction. In the CERAD, the IPD patients exhibited deficits in non-verbal memory, attention, psychomotor velocity, visuoconstructive ability, and executive functions. After Bonferroni correction for multiple comparisons, we found significant correlations between performance of the CERAD subtests Boston Naming Test (a specific test for visual perception and for detection of word-finding difficulties) and Word List Intrusions (a specific test for learning capacity and memory for language information) vs binding of α4β2 nAchR in cortical (the right superior parietal lobule) and subcortical areas (the left thalamus, the left posterior subcortical region, and the right posterior subcortical region). These significant correlations between the results of the CERAD subtests and the cerebral α4β2 nAchR density, as assessed by 5-I-A-85380 SPECT, indicate that cerebral cholinergic pathways are relevant to cognitive processing in IPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Applications of iQID cameras

NASA Astrophysics Data System (ADS)

Han, Ling; Miller, Brian W.; Barrett, Harrison H.; Barber, H. Bradford; Furenlid, Lars R.

2017-09-01

iQID is an intensified quantum imaging detector developed in the Center for Gamma-Ray Imaging (CGRI). Originally called BazookaSPECT, iQID was designed for high-resolution gamma-ray imaging and preclinical gamma-ray single-photon emission computed tomography (SPECT). With the use of a columnar scintillator, an image intensifier and modern CCD/CMOS sensors, iQID cameras features outstanding intrinsic spatial resolution. In recent years, many advances have been achieved that greatly boost the performance of iQID, broadening its applications to cover nuclear and particle imaging for preclinical, clinical and homeland security settings. This paper presents an overview of the recent advances of iQID technology and its applications in preclinical and clinical scintigraphy, preclinical SPECT, particle imaging (alpha, neutron, beta, and fission fragment), and digital autoradiography.

Reduced striatal D2 receptor binding in myoclonus-dystonia.

PubMed

Beukers, R J; Booij, J; Weisscher, N; Zijlstra, F; van Amelsvoort, T A M J; Tijssen, M A J

2009-02-01

To study striatal dopamine D(2) receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D(2) receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I SPECT/CT for accurate staging.

PubMed

Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar

2014-11-01

Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.

Scatter and crosstalk corrections for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Peng; Hutton, Brian F.; Holstensson, Maria

2015-12-15

Purpose: The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). Methods: A tailing model was developed to account for the low energy tail effectsmore » of the CZT detector. The parameters of the model were obtained using {sup 99m}Tc and {sup 123}I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. Results: Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of {sup 99m}Tc in dual-radionuclide imaging where there is heavy contamination from {sup 123}I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of {sup 99m}Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. Conclusions: The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.« less

Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kita, Ayako; Higa, Mari; Doi, Akira

Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis withmore » multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.« less

SPECT/CT demonstrating 131I retention in Warthin tumor on thyroid cancer survey scan.

PubMed

Zhang, Yuyang; Minoshima, Satoshi

2013-09-01

A 48-year-old male patient of papillary thyroid cancer, status post-thyroidectomy and node dissection, was referred to (131)I scan prior to radioiodine treatment. The images showed 1 additional focus of (131)I uptake in the right upper neck outside of the thyroid bed. SPECT/CT demonstrated 2 separate foci of radioiodine uptake in the right parotid gland, instead of neck lymph nodes. Diagnostic CT showed 2 corresponding soft tissue nodules in the right parotid gland which were confirmed latter by fine-needle aspiration to be Warthin tumors. This case illustrates a pivotal role of SPECT/CT in differential diagnosis of abnormal neck uptake on (131)I thyroid cancer scan.

High-resolution clustered pinhole (131)Iodine SPECT imaging in mice.

PubMed

van der Have, Frans; Ivashchenko, Oleksandra; Goorden, Marlies C; Ramakers, Ruud M; Beekman, Freek J

2016-08-01

High-resolution pre-clinical (131)I SPECT can facilitate development of new radioiodine therapies for cancer. To this end, it is important to limit resolution-degrading effects of pinhole edge penetration by the high-energy γ-photons of iodine. Here we introduce, optimize and validate (131)I SPECT performed with a dedicated high-energy clustered multi-pinhole collimator. A SPECT-CT system (VECTor/CT) with stationary gamma-detectors was equipped with a tungsten collimator with clustered pinholes. Images were reconstructed with pixel-based OSEM, using a dedicated (131)I system matrix that models the distance- and energy-dependent resolution and sensitivity of each pinhole, as well as the intrinsic detector blurring and variable depth of interaction in the detector. The system performance was characterized with phantoms and in vivo static and dynamic (131)I-NaI scans of mice. Reconstructed image resolution reached 0.6mm, while quantitative accuracy measured with a (131)I filled syringe reaches an accuracy of +3.6±3.5% of the gold standard value. In vivo mice scans illustrated a clear shape of the thyroid and biodistribution of (131)I within the animal. Pharmacokinetics of (131)I was assessed with 15-s time frames from the sequence of dynamic images and time-activity curves of (131)I-NaI. High-resolution quantitative and fast dynamic (131)I SPECT in mice is possible by means of a high-energy collimator and optimized system modeling. This enables analysis of (131)I uptake even within small organs in mice, which can be highly valuable for development and optimization of targeted cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment.

PubMed

Burlison, Jared S; Hartshorne, Michael F; Voda, Alan M; Cocks, Franklin H; Fair, Joanna R

2013-12-01

We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 131I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1-16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of I from Argenco HP 77. SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals.

123I-IPPA SPECT for the prediction of enhanced left ventricular function after coronary bypass graft surgery. Multicenter IPPA Viability Trial Investigators. 123I-iodophenylpentadecanoic acid.

PubMed

Verani, M S; Taillefer, R; Iskandrian, A E; Mahmarian, J J; He, Z X; Orlandi, C

2000-08-01

Fatty acids are the prime metabolic substrate for myocardial energy production. Hence, fatty acid imaging may be useful in the assessment of myocardial hibernation. The goal of this prospective, multicenter trial was to assess the use of a fatty acid, 123I-iodophenylpentadecanoic acid (IPPA), to identify viable, hibernating myocardium. Patients (n = 119) with abnormal left ventricular wall motion and a left ventricular ejection fraction (LVEF) < 40% who were already scheduled to undergo coronary artery bypass grafting (CABG) underwent IPPA tomography (rest and 30-min redistribution) and blood-pool radionuclide angiography within 3 d of the scheduled operation. Radionuclide angiography was repeated 6-8 wk after CABG. The study endpoint was a > or =10% increase in LVEF after CABG. The number of IPPA-viable abnormally contracting segments necessary to predict a positive LVEF outcome was determined by receiver operating characteristic (ROC) curves and was included in a logistic regression analysis, together with selected clinical variables. Before CABG, abnormal IPPA tomography findings were seen in 113 of 119 patients (95%), of whom 71 (60%) had redistribution in the 30-min images. The LVEF increased modestly after CABG (from 32% +/- 12% to 36% +/- 8%, P< 0.001).A > or =10% increase in LVEF after CABG occurred in 27 of 119 patients (23%). By ROC curves, the best predictor of a > or =10% increase in LVEF was the presence of > or =7 IPPA-viable segments (accuracy, 72%; confidence interval, 64%-80%). Among clinical and scintigraphic variables, the single most important predictor also was the number of IPPA-viable segments (P = 0.008). The number of IPPA-viable segments added significant incremental value to the best clinical predictor model. Asubstantial increase in LVEF occurs after CABG in only a minority of patients (23%) with depressed preoperative function. The number of IPPA-viable segments is useful in predicting a clinically meaningful increase in LVEF.

IMP I, H, and J

NASA Technical Reports Server (NTRS)

1973-01-01

The schedule for the IMP project for the eighth, ninth, and tenth satellites of the series is presented. A description of the spacecraft and the weekly summaries of the operations performed on the spacecraft are provided. The project planning, project problems, recommendations, and reports of launch operations are described. Drawings of the satellite structures are included.

Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa.

PubMed

Kazmierczak, Krystyna M; Rabine, Sharon; Hackel, Meredith; McLaughlin, Robert E; Biedenbach, Douglas J; Bouchillon, Samuel K; Sahm, Daniel F; Bradford, Patricia A

2016-02-01

Metallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were characterized for bla genes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses): P. aeruginosa (308), Klebsiella spp. (85), Enterobacter spp. (39), Proteeae (16), Citrobacter freundii (12), Escherichia coli (6), and Serratia marcescens (5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). The in vitro activities of all tested antibiotics against MBL-positive Enterobacteriaceae were significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml), whereas colistin was the most effective agent against MBL-positive P. aeruginosa isolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

PubMed Central

Rabine, Sharon; Hackel, Meredith; McLaughlin, Robert E.; Biedenbach, Douglas J.; Bouchillon, Samuel K.; Sahm, Daniel F.; Bradford, Patricia A.

2015-01-01

Metallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were characterized for bla genes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses): P. aeruginosa (308), Klebsiella spp. (85), Enterobacter spp. (39), Proteeae (16), Citrobacter freundii (12), Escherichia coli (6), and Serratia marcescens (5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). The in vitro activities of all tested antibiotics against MBL-positive Enterobacteriaceae were significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml), whereas colistin was the most effective agent against MBL-positive P. aeruginosa isolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning. PMID:26643349

System Integration of FastSPECT III, a Dedicated SPECT Rodent-Brain Imager Based on BazookaSPECT Detector Technology

PubMed Central

Miller, Brian W.; Furenlid, Lars R.; Moore, Stephen K.; Barber, H. Bradford; Nagarkar, Vivek V.; Barrett, Harrison H.

2010-01-01

FastSPECT III is a stationary, single-photon emission computed tomography (SPECT) imager designed specifically for imaging and studying neurological pathologies in rodent brain, including Alzheimer’s and Parkinsons’s disease. Twenty independent BazookaSPECT [1] gamma-ray detectors acquire projections of a spherical field of view with pinholes selected for desired resolution and sensitivity. Each BazookaSPECT detector comprises a columnar CsI(Tl) scintillator, image-intensifier, optical lens, and fast-frame-rate CCD camera. Data stream back to processing computers via firewire interfaces, and heavy use of graphics processing units (GPUs) ensures that each frame of data is processed in real time to extract the images of individual gamma-ray events. Details of the system design, imaging aperture fabrication methods, and preliminary projection images are presented. PMID:21218137

Predominance of carbapenem-resistant Pseudomonas aeruginosa isolates carrying blaIMP and blaVIM metallo-β-lactamases in a major hospital in Costa Rica.

PubMed

Toval, Francisco; Guzmán-Marte, Anel; Madriz, Vivian; Somogyi, Teresita; Rodríguez, César; García, Fernando

2015-01-01

This study aimed to assess the molecular basis of the resistance to carbapenems in clinical isolates of Pseudomonas aeruginosa recovered from a tertiary-level health facility in San José, Costa Rica. A total of 198 non-duplicated isolates were evaluated for their susceptibility to β-lactams, aminoglycosides and fluoroquinolones. The production of metallo-β-lactamases (MBLs), the presence of MBL encoding genes (blaIMP, blaVIM and blaGIM-1) and the occurrence of these genes within class 1 integrons were investigated. In addition, an ERIC2 PCR fingerprinting method was used to elucidate the distribution of the detected MBL genes within the strain collection. Of the 198 isolates tested, 125 (63.1 %) were categorized as carbapenem-resistant. The majority (88.8 %) of the carbapemen-resistant isolates also showed resistance to ceftazidime, cefepime, aztreonam, ticarcillin/clavulanic acid, amikacin, gentamicin, tobramycin, ciprofloxacin and gatifloxacin. Among the carbapenem-resistant isolates, 102 (81.6 %) showed MBL activity. Strikingly, both blaIMP and blaVIM genes were simultaneously detected in most (94.1 %) of the 102 MBL producers. Five carbapenem-resistant MBL producers were positive only for blaIMP genes. Almost 70 % of the isolates examined harboured the intI1 gene, accompanied by the sul1 and qacEΔ1 genes in 136 (99 %) and 122 (89 %) isolates, respectively. The majority (94.4 %) of the carbapenem-resistant isolates carried the intI1 gene, in contrast to 26 % of the carbapenem-susceptible isolates. Ninety-three out of 96 (96.9 %) isolates carrying both blaIMP and blaVIM genes also harboured the intI1, sul1 and qacEΔ1 genes. Gene cassettes from carbapenem-susceptible and MBL-negative carbapenem-resistant isolates encoded aminoglycoside-resistance enzymes (aadA2, aadA4 and aadA6) as well as orfD and qacF genes. RAPD analysis distributed 126 of the isolates in 29 clusters. Eighty of the 90 blaIMP (+) blaVIM (+) isolates were sorted into 16 different clusters, suggesting that the blaIMP and blaVIM genes detected were located within a genetic element capable of lateral transfer. Carbapenem-resistant MBL-positive isolates were recovered from almost all hospital wards and were over-represented in samples obtained from the surgical emergency and intensive care therapy units. Remarkably, three carbapenem-resistant isolates, exhibiting MBL activity and carrying both blaIMP and blaVIM genes, were recovered from outpatients. Sequence analysis of both bla genes in various isolates revealed that they correspond to the alleles blaIMP-18 and blaVIM-2. To our knowledge, this is the first report of the combination of two metallo-β-lactamases encoded by the blaIMP-18 and blaVIM-2 genes in P. aeruginosa. © 2015 The Authors.

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

PubMed Central

Vines, Douglass C.; Scollard, Deborah A.; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Besanger, Travis

2017-01-01

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy. PMID:29097943

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

PubMed

Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

2017-01-01

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.

SU-E-I-20: Dead Time Count Loss Compensation in SPECT/CT: Projection Versus Global Correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siman, W; Kappadath, S

Purpose: To compare projection-based versus global correction that compensate for deadtime count loss in SPECT/CT images. Methods: SPECT/CT images of an IEC phantom (2.3GBq 99mTc) with ∼10% deadtime loss containing the 37mm (uptake 3), 28 and 22mm (uptake 6) spheres were acquired using a 2 detector SPECT/CT system with 64 projections/detector and 15 s/projection. The deadtime, Ti and the true count rate, Ni at each projection, i was calculated using the monitor-source method. Deadtime corrected SPECT were reconstructed twice: (1) with projections that were individually-corrected for deadtime-losses; and (2) with original projections with losses and then correcting the reconstructed SPECTmore » images using a scaling factor equal to the inverse of the average fractional loss for 5 projections/detector. For both cases, the SPECT images were reconstructed using OSEM with attenuation and scatter corrections. The two SPECT datasets were assessed by comparing line profiles in xyplane and z-axis, evaluating the count recoveries, and comparing ROI statistics. Higher deadtime losses (up to 50%) were also simulated to the individually corrected projections by multiplying each projection i by exp(-a*Ni*Ti), where a is a scalar. Additionally, deadtime corrections in phantoms with different geometries and deadtime losses were also explored. The same two correction methods were carried for all these data sets. Results: Averaging the deadtime losses in 5 projections/detector suffices to recover >99% of the loss counts in most clinical cases. The line profiles (xyplane and z-axis) and the statistics in the ROIs drawn in the SPECT images corrected using both methods showed agreement within the statistical noise. The count-loss recoveries in the two methods also agree within >99%. Conclusion: The projection-based and the global correction yield visually indistinguishable SPECT images. The global correction based on sparse sampling of projections losses allows for accurate SPECT deadtime loss correction while keeping the study duration reasonable.« less

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection.

PubMed

Kojima, Akihiro; Gotoh, Kumiko; Shimamoto, Masako; Hasegawa, Koki; Okada, Seiji

2016-02-01

Iodine-131 is widely used for radionuclide therapy because of its β-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV). The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned. Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image. We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

Simulation study of the second-generation MR-compatible SPECT system based on the inverted compound-eye gamma camera design

NASA Astrophysics Data System (ADS)

Lai, Xiaochun; Meng, Ling-Jian

2018-02-01

In this paper, we present simulation studies for the second-generation MRI compatible SPECT system, MRC-SPECT-II, based on an inverted compound eye (ICE) gamma camera concept. The MRC-SPECT-II system consists of a total of 1536 independent micro-pinhole-camera-elements (MCEs) distributed in a ring with an inner diameter of 6 cm. This system provides a FOV of 1 cm diameter and a peak geometrical efficiency of approximately 1.3% (the typical levels of 0.1%-0.01% found in modern pre-clinical SPECT instrumentations), while maintaining a sub-500 μm spatial resolution. Compared to the first-generation MRC-SPECT system (MRC-SPECT-I) (Cai 2014 Nucl. Instrum. Methods Phys. Res. A 734 147-51) developed in our lab, the MRC-SPECT-II system offers a similar resolution with dramatically improved sensitivity and greatly reduced physical dimension. The latter should allow the system to be placed inside most clinical and pre-clinical MRI scanners for high-performance simultaneous MRI and SPECT imaging.

Dimensions of disinhibited personality and their relation with alcohol use and problems

PubMed Central

Gunn, Rachel L.; Finn, Peter R.; Endres, Michael J.; Gerst, Kyle R.; Spinola, Suzanne

2013-01-01

Although alcohol use disorders (AUDs) have been associated with different aspects of disinhibited personality and antisociality, less is known about the specific relationships among different domains of disinhibited personality, antisociality, alcohol use, and alcohol problems. The current study was designed to address three goals, (i) to provide evidence of a three-factor model of disinhibited personality (comprised of impulsivity [IMP], risk taking/ low harm avoidance [RTHA], excitement seeking [ES]), (ii) to test hypotheses regarding the association between each dimension and alcohol use and problems, and (iii) to test the hypothesis that antisociality (social deviance proneness [SDP]) accounts for the direct association between IMP and alcohol problems, while ES is directly related to alcohol use. Measures of disinhibited personality IMP, RTHA, ES and SDP and alcohol use and problems were assessed in a sample of young adults (N=474), which included a high proportion of individuals with AUDs. Confirmatory factor analyses supported a three-factor model of disinhibited personality reflecting IMP, RTHA, and ES. A structural equation model (SEM) showed that IMP was specifically associated with alcohol problems, while ES was specifically associated with alcohol use. In a second SEM, SDP accounted for the majority of the variance in alcohol problems associated with IMP. The results suggest aspects of IMP associated with SDP represent a direct vulnerability to alcohol problems. In addition, the results suggest that ES reflects a specific vulnerability to excessive alcohol use, which is then associated with alcohol problems, while RTHA is not specifically associated with alcohol use or problems when controlling for IMP and ES. PMID:23588138

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, Katherine L.; Judenhofer, Martin S.; Cherry, Simon R.

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. Furthermore, such high-resolution systems have relatively poor sensitivity (typically 0.01% to 0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatialmore » resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO 4- xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. In conclusion, UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.« less

The diagnostic utility of 3D-ESI rotating and moving dipole methodology in the pre-surgical evaluation of MRI-negative childhood epilepsy due to focal cortical dysplasia.

PubMed

Russo, Angelo; Lallas, Matt; Jayakar, Prasanna; Miller, Ian; Hyslop, Ann; Dunoyer, Catalina; Resnick, Trevor; Duchowny, Michael

2016-09-01

This study investigates whether a combined rotating dipole (RD) and moving dipole (MD) solution enhances three-dimensional electroencephalography (EEG) source imaging (3D-ESI) localization in magnetic resonance imaging (MRI)-negative pediatric patients with focal cortical dysplasia (FCD). We retrospectively selected 14 MRI-negative patients with FCD from a cohort of 60 pediatric patients previously used to evaluate the diagnostic utility of 3D-ESI in epilepsy surgery. Patients were younger than 18 years at time of surgery and had at least 1 year of outcome data. RD and MD models were constructed for each interictal spike or sharp wave, and it was determined whether each inverse algorithm localized within the surgical resection cavity (SRC). We also compared the 3D-ESI findings and surgical outcome with positron emission tomography (PET) and ictal single photon emission computed tomography (iSPECT). RD analyses revealed a high concordance with the SRC (78.6%), particularly for temporal lobe resection (100.0%), and showed superior localization compared to PET and iSPECT, with the highest correlation in FCD type I and temporal lobe resection. Furthermore, the RD method was superior to iSPECT in FCD type II cases and to PET in extratemporal resections. RD and MD results were comparable, but in 18.2% of patients with FCD type I with localizing RDs, the MD solution was only partially within the SRC; in all of these patients 3D-ESI also correlated with superior surgical outcome compared to PET and iSPECT, especially when RD and MD solutions were analyzed together. 3D-ESI in MRI-negative cases showed superior localization compared to iSPECT or PET, especially in FCD type I and temporal lobe epilepsy, and correlated with superior surgical outcome compared to iSPECT and PET at 1 year and 2 years postoperatively, especially when RD and MD solutions were analyzed together. These findings suggest that 3D-ESI based on a combined RD-MD solution improves surgical accuracy in MRI-negative patients with FCD. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Detection of novel cancer-testis antigen-specific T-cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma.

PubMed

Mizukami, Yoshiki; Kono, Koji; Daigo, Yataro; Takano, Atsushi; Tsunoda, Takuya; Kawaguchi, Yoshihiko; Nakamura, Yusuke; Fujii, Hideki

2008-07-01

We recently identified three HLA-A2402-restricted epitope peptides derived from cancer-testis antigens (CTA), TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3) for the development of immunotherapies against esophageal squamous cell carcinoma (ESCC). In order to evaluate their immunotherapeutic potential in ESCC patients, we estimated by ELISPOT assay the TTK-, LY6K-, or IMP-3-specific T-cell immune responses in tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) expanded from 20HLA-A2402 (+) ESCC patients, and correlated their immune activity with the expression levels of TTK, LY6K, and IMP-3, and MHC class I in the tumors. Induction of TTK-antigen specific T-cell response in TIL to the peptide-pulsed target cells was detected in 14 out of 20 (70%) cases, while LY6K or IMP-3 specific T-cell activity was observed in 11 of 20 (55%) or in eight of 20 (40%) cases, respectively. Furthermore, T-cell activity in RLNL and PBL was detectable in the similar proportion of the 20 ESCC patients. Interestingly, CTA-specific T-cell immune response was found in 13 of 14 (93%) TIL obtained from ESCC tumors with strong MHC class I expression, while it could be observed only in two of six (33%) TIL from ESCC tumors with weak MHC class I expression. These results strongly suggest the pre-existence of specific T-cell responses to HLA-A24-restricted epitope peptides from TTK, LY6K, and IMP-3 in ESCC patients. Monitoring antigen-specific T-cell responses, as well as the expression levels of MHC class I and epitope CTA in tumors, should be a selection index for application of cancer vaccine therapies to the patients who are likely to show good immune response.

Cyclotron production of I-123: An evaluation of the nuclear reactions which produce this isotope

NASA Technical Reports Server (NTRS)

Sodd, V. J.; Scholz, K. L.; Blue, J. W.; Wellamn, H. N.

1970-01-01

The reactions studied which produce I-123 directly were Sb-121(He-4,2n) I-123, Sb-121(He-3,n) I-123, Te-122(d,n) I-123, Te-122(He-4,p2n) I-123, Te-122(He-3,pn) I-123, and Te-123(He-3,p2n) I-123. Reactions which produce I-123 indirectly through the positron decay of 2.1-hour Xe-123 were Te-122(He-4,3n) Xe-123, Te-122(He-3,2n) Xe-123 and Te-123(He-3,3n) Xe-123. Use of the gas flow I-123 cyclotron target assembly is recommended for the production of I-123 with radiochemical purity greater than 99.995%.

Imaging genetics approach to predict progression of Parkinson's diseases.

PubMed

Mansu Kim; Seong-Jin Son; Hyunjin Park

2017-07-01

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123 I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

National cyclotron centre at the Institute for Nuclear Research and Nuclear Energy

NASA Astrophysics Data System (ADS)

Tonev, D.; Goutev, N.; Asova, G.; Artinyan, A.; Demerdjiev, A.; Georgiev, L. S.; Yavahchova, M.; Bashev, V.; Genchev, S. G.; Geleva, E.; Mincheva, M.; Nikolov, A.; Dimitrov, D. T.

2018-05-01

An accelerator laboratory is presently under construction in Sofia at the Institute for Nuclear Research and Nuclear Energy. The laboratory will use a TR24 type of cyclotron, which provides a possibility to accelerate a proton beam with an energy of 15 to 24 MeV and current of up to 0.4 mA. An accelerator with such parameters allows to produce a large variety of radioisotopes for development of radiopharmaceuticals. The most common radioisotopes that can be produced with such a cyclotron are PET isotopes like: 11C, 13N, 15O, 18F, 124I, 64Cu, 68Ge/68Ga, and SPECT isotopes like: 123I, 111In, 67Ga, 57Co, 99mTc. Our aim is to use the cyclotron facility for research in the fields of radiopharmacy, radiochemistry, radiobiology, nuclear physics, materials sciences, applied research, new materials and for education in all these fields including nuclear energy. Presently we perform investigations in the fields of target design for production of radioisotopes, shielding and radioprotection, new ion sources etc.

Cancer imaging with CEA antibodies: historical and current perspectives.

PubMed

Goldenberg, D M

1992-01-01

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lever, J.R.; Scheffel, U.; Stathis, M.

Analogues of diprenorphine (DPN) having C6-O-iodoallyl (O-IA-DPN) and N-iodoallyl (N-IA-DPN) substituents can be I-125 labeled in good yield with high specific activity by radioiododestannylation. When tested in vitro against [H-3]-DPN in rat brain membranes, the apparent affinity (Ki) of O-IA-DPN (1.35 nM) proved 17-fold stronger than that of N-IA-DPN (23.4 nM). Against selective [H-3]-ligands, O-IA-DPN showed high apparent affinities for {mu}(1.9 nM), {gamma}(1.1 nM) and {kappa}(0.9 nM) sites. Consistent with the low apparent affinity in vitro, [I-125]-N-IA- DPN did not allow localization of cerebral opioid receptors after i.v. administration to mice. By contrast, [I-125]-O-IA-DPN exhibited a regional brain distribution whichmore » reflects binding to multiple opioid receptors. The highest radioactivity concentrations were in superior colliculi, hypothalamus, olfactory tubercles, thalamus and striatum. Peak levels (2.5-3.5 %ID/g) were maintained over the first 60 min. At all times, the lowest levels of radioactivity were in the cerebellum. Binding in vivo was saturable by O-IA-DPN, was blocked by (-)- but not by (+)-naloxone, and was inhibited by naltrexone in dose-dependent fashion. Specific binding was 83-93% for all tissues except cerebellum, where 50% blockade was noted with naltrexone (5.0 mg/kg). Using naltrexone blockade to define non-specific binding, the highest ratio of specific to non-specific binding (> 14 to 1) was noted for superior colliculi at 60 min. Inhibition studies with drugs selective for {mu}, {gamma} or {kappa} sites established that multiple opioid receptors are labeled. [123I]-O-IA-DPN has been prepared (84%, >2400 mCi/{mu}mol), and allows visualization of opioid receptors in mouse brain by ex vivo autoradiography. Together, these results suggest that [123I]-O-IA-DPN is suitable for SPECT studies of multiple opioid receptors.« less

A parallel Monte Carlo code for planar and SPECT imaging: implementation, verification and applications in (131)I SPECT.

PubMed

Dewaraja, Yuni K; Ljungberg, Michael; Majumdar, Amitava; Bose, Abhijit; Koral, Kenneth F

2002-02-01

This paper reports the implementation of the SIMIND Monte Carlo code on an IBM SP2 distributed memory parallel computer. Basic aspects of running Monte Carlo particle transport calculations on parallel architectures are described. Our parallelization is based on equally partitioning photons among the processors and uses the Message Passing Interface (MPI) library for interprocessor communication and the Scalable Parallel Random Number Generator (SPRNG) to generate uncorrelated random number streams. These parallelization techniques are also applicable to other distributed memory architectures. A linear increase in computing speed with the number of processors is demonstrated for up to 32 processors. This speed-up is especially significant in Single Photon Emission Computed Tomography (SPECT) simulations involving higher energy photon emitters, where explicit modeling of the phantom and collimator is required. For (131)I, the accuracy of the parallel code is demonstrated by comparing simulated and experimental SPECT images from a heart/thorax phantom. Clinically realistic SPECT simulations using the voxel-man phantom are carried out to assess scatter and attenuation correction.

A restraint-free small animal SPECT imaging system with motion tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisenberger, A.G.; Gleason, S.S.; Goddard, J.

2005-06-01

We report on an approach toward the development of a high-resolution single photon emission computed tomography (SPECT) system to image the biodistribution of radiolabeled tracers such as Tc-99m and I-125 in unrestrained/unanesthetized mice. An infrared (IR)-based position tracking apparatus has been developed and integrated into a SPECT gantry. The tracking system is designed to measure the spatial position of a mouse's head at a rate of 10-15 frames per second with submillimeter accuracy. The high-resolution, gamma imaging detectors are based on pixellated NaI(Tl) crystal scintillator arrays, position-sensitive photomultiplier tubes, and novel readout circuitry requiring fewer analog-digital converter (ADC) channels whilemore » retaining high spatial resolution. Two SPECT gamma camera detector heads based upon position-sensitive photomultiplier tubes have been built and installed onto the gantry. The IR landmark-based pose measurement and tracking system is under development to provide animal position data during a SPECT scan. The animal position and orientation data acquired by the tracking system will be used for motion correction during the tomographic image reconstruction.« less

Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma.

PubMed

Wong, K K; Zarzhevsky, N; Cahill, J M; Frey, K A; Avram, A M

2009-10-01

Hybrid imaging modalities such as radioiodine single photon emission CT with integrated CT ((131)I SPECT-CT) and 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography with integrated CT (FDG PET-CT) allow the rapid and efficient fusion of functional and anatomic images, and provide diagnostic information that may influence management decisions in patients with differentiated thyroid carcinoma (DTC). Diagnostic localisation and therapy of these tumours are dependent upon their capacity to concentrate radioiodine ((131)I) via uptake through the sodium-iodide symporter and retention within the tumour. The prognosis for most patients with DTC is favourable, although controversy exists regarding the role of post-operative (131)I therapy in patients at low-risk for disease. Accurate identification of functional thyroid tissue (benign or malignant) using diagnostic (131)I planar scintigraphy complemented by SPECT-CT imaging enables the completion of post-operative staging and patient risk stratification prior to (131)I therapy administration. In patients with non-iodine-avid tumours (negative (131)I scan but elevated thyroglobulin indicative of persistent or recurrent disease), FDG PET-CT is used to identify tumours with enhanced glucose metabolism and to localise the source of thyroglobulin production. The CT component of this hybrid technology provides anatomic localisation of activity and allows CT-based attenuation correction of PET images. Images from 15 patients illustrate the applications of (131)I SPECT-CT and FDG PET-CT.

The Arbitrary Body of Revolution Code (ABORC) for SGEMP/IEMP

DTIC Science & Technology

1976-07-01

Ill, ,4 t iwv. dependent Spect ria, I’a eallt rlllt ,ýcltllt i , itlld currll - in.icct iwill silIkit ion tests of satel I ites. "S1 1’. Waanaasl ; et...time. For example, in the case where the emission is due to,. photon interaction with materials, the photon energy and time spect run determines the...ally performed by separating the i. onse of the in-._ tn, p rtion of ’he problem from thai of the external iort(n. Thus, 0i details of tbi - internal

Radiolabeled cyclic arginine-glycine-aspartic (RGD)-conjugated iron oxide nanoparticles as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer

NASA Astrophysics Data System (ADS)

Deng, Shengming; Zhang, Wei; Zhang, Bin; Hong, Ruoyu; Chen, Qing; Dong, Jiajia; Chen, Yinyiin; Chen, Zhiqiang; Wu, Yiwei

2015-01-01

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) modified with a novel cyclic arginine-glycine-aspartate (RGD) peptide were made and radiolabeled as single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) dual-modality agents for imaging of breast cancer. The probe was tested both in vitro and in vivo to determine its receptor targeting efficacy and feasibility for SPECT and MRI. The radiochemical syntheses of 125I-cRGD-USPIO were accomplished with a radiochemical purity of 96.05 ± 0.33 %. High radiochemical stability was found in fresh human serum and in phosphate-buffered saline. The average hydrodynamic size of 125I-cRGD-USPIO determined by dynamic light scattering was 51.3 nm. Results of in vitro experiments verified the specificity of the radiolabeled nanoparticles to tumor cells. Preliminary biodistribution studies of 125I-radiolabeled cRGD-USPIO in Bcap37-bearing nude mice showed that it had long circulation half-life, high tumor uptake, and high initial blood retention with moderate liver uptake. In vivo tumor targeting and uptake of the radiolabeled nanoparticles in mice model were visualized by SPECT and MRI collected at different time points. Our results strongly indicated that the 125I-cRGD-USPIO could be used as a promising bifunctional radiotracer for early clinical tumor detection with high sensitivity and high spatial resolution by SPECT and MRI.

Physics process level discrimination of detections for GATE: assessment of contamination in SPECT and spurious activity in PET.

PubMed

De Beenhouwer, Jan; Staelens, Steven; Vandenberghe, Stefaan; Verhaeghe, Jeroen; Van Holen, Roel; Rault, Erwann; Lemahieu, Ignace

2009-04-01

The GEANT4 application for tomographic emission (GATE) is one of the most detailed Monte Carlo simulation tools for SPECT and PET. It allows for realistic phantoms, complex decay schemes, and a large variety of detector geometries. However, only a fraction of the information in each particle history is available for postprocessing. In order to extend the analysis capabilities of GATE, a flexible framework was developed. This framework allows all detected events to be subdivided according to their type: In PET, true coincidences from others, and in SPECT, geometrically collimated photons from others. The framework of the authors can be applied to any isotope, phantom, and detector geometry available in GATE. It is designed to enhance the usability of GATE for the study of contamination and for the investigation of the properties of current and future prototype detectors. The authors apply the framework to a case study of Bexxar, first assuming labeling with 124I, then with 131I. It is shown that with 124I PET, results with an optimized window improve upon those with the standard window but achieve less than half of the ideal improvement. Nevertheless, 124I PET shows improved resolution compared to 131I SPECT with triple-energy-window scatter correction.

Effect of Sea Buckthorn Leaves on Inosine Monophosphate and Adenylosuccinatelyase Gene Expression in Broilers during Heat Stress.

PubMed

Zhao, Wei; Chen, Xin; Yan, Changjiang; Liu, Hongnan; Zhang, Zhihong; Wang, Pengzu; Su, Jie; Li, Yao

2012-01-01

The trial was conducted to evaluate the effects of sea buckthorn leaves (SBL) on meat flavor in broilers during heat stress. A total 360 one-day-old Arbor Acre (AA) broilers (male) were randomly allotted to 4 treatments with 6 replicates pens pretreatment and 15 birds per pen. The control group was fed a basal diet, the experimental group I, II and III were fed the basal diet supplemented with 0.25%, 0.5%, 1% SBL, respectively. During the 4th week, broilers were exposed to heat stress conditions (36±2°C), after which, muscle and liver samples were collected. High performance liquid chromatography (HPLC) was performed to measure the content of inosine monophosphate (IMP); Real-Time PCR was performed to determine the expression of the ADSL gene. The results showed that the content of breast muscle IMP of group I, II and III was significantly increased 68%, 102% and 103% (p<0.01) compared with the control, respectively; the content of thigh muscle IMP of group II and III was significantly increased 56% and 58% (p<0.01), respectively. Additionally, ADSL mRNA expression in group I, II and III was increased significantly 80%, 65% and 49% (p<0.01) compared with the control, respectively. The content of IMP and expression of ADSL mRNA were increased by basal diet supplemented with SBL, therefore, the decrease of meat flavor caused by heat stress was relieved.

Membrane protein stability can be compromised by detergent interactions with the extramembranous soluble domains

PubMed Central

Yang, Zhengrong; Wang, Chi; Zhou, Qingxian; An, Jianli; Hildebrandt, Ellen; Aleksandrov, Luba A; Kappes, John C; DeLucas, Lawrence J; Riordan, John R; Urbatsch, Ina L; Hunt, John F; Brouillette, Christie G

2014-01-01

Detergent interaction with extramembranous soluble domains (ESDs) is not commonly considered an important determinant of integral membrane protein (IMP) behavior during purification and crystallization, even though ESDs contribute to the stability of many IMPs. Here we demonstrate that some generally nondenaturing detergents critically destabilize a model ESD, the first nucleotide-binding domain (NBD1) from the human cystic fibrosis transmembrane conductance regulator (CFTR), a model IMP. Notably, the detergents show equivalent trends in their influence on the stability of isolated NBD1 and full-length CFTR. We used differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy to monitor changes in NBD1 stability and secondary structure, respectively, during titration with a series of detergents. Their effective harshness in these assays mirrors that widely accepted for their interaction with IMPs, i.e., anionic > zwitterionic > nonionic. It is noteworthy that including lipids or nonionic detergents is shown to mitigate detergent harshness, as will limiting contact time. We infer three thermodynamic mechanisms from the observed thermal destabilization by monomer or micelle: (i) binding to the unfolded state with no change in the native structure (all detergent classes); (ii) native state binding that alters thermodynamic properties and perhaps conformation (nonionic detergents); and (iii) detergent binding that directly leads to denaturation of the native state (anionic and zwitterionic). These results demonstrate that the accepted model for the harshness of detergents applies to their interaction with an ESD. It is concluded that destabilization of extramembranous soluble domains by specific detergents will influence the stability of some IMPs during purification. PMID:24652590

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

PubMed

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-02-01

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion syndrome and subjects at ultra high-risk for psychosis.

PubMed

Vingerhoets, Claudia; Bloemen, Oswald J N; Boot, Erik; Bakker, Geor; de Koning, Mariken B; da Silva Alves, Fabiana; Booij, Jan; van Amelsvoort, Thérèse A M J

2018-02-28

Striatal dopamine (DA) dysfunction has been consistently reported in psychotic disorders. Differences and similarities in the pathogenesis between populations at clinical and genetic risk for developing psychosis are yet to be established. Here we explored markers of dopamine (DA) function in subjects meeting clinically ultra-high risk criteria for psychosis (UHR) and in subjects with 22q11.2 deletion syndrome (22q11DS), a genetic condition associated with significant risk for developing psychotic disorders. Single Photon Emission Computed Tomography (SPECT) with 123 I-labelled iodobenzamide ([ 123 I]IBZM) was used to measure striatal DA D 2/3 receptor binding potential (D 2 R BP ND ). Also, peripheral DAergic markers were assessed in serum and urine (plasma prolactin (pPRL), plasma homovanillic acid (pHVA) and urine DA(uDA)). No significant difference in striatal D 2 R BP ND was found between UHR and 22q11DS subjects. Compared to UHR subjects, pPRL and pHVA were lower and uDA levels were higher in the 22q11DS subjects. However, after correcting for age and gender, only pPRL as significantly lower in the 22q11DS patients. These results may suggest that there are differences in DAergic markers between subjects with UHR and with 22q11DS that may reflect differences in the pathways to psychosis. However, bigger samples are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

PubMed Central

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-01-01

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications. PMID:23899625

[Evaluation of left ventricular perfusion and regional wall motion in myocardial infarction: using 201Tl myocardial SPECT and 99mTc-HSAD multigated cardiac blood pool emission computed tomography].

PubMed

Nanjyo, S

1994-09-01

In order to evaluate left ventricular regional wall motion and regional myocardial perfusion, 99mTc-HSAD multigated cardiac blood pool emission computed tomography (cardiac pool SPECT) and 201Tl myocardial SPECT (Tl) were performed on 12 patients with acute myocardial infarction (AMI), 6 patients had treated with only thrombolysis in group I and 6 patients had treated with thrombolysis and selective PTCA in group II, 17 patients with old myocardial infarction (OMI) in group III and 5 normal volunteers (controls). The relationship between left ventricular regional wall motion and regional myocardial perfusion was estimated. The relationship between % length shortening (%LS) by cardiac pool SPECT and %Tl uptake (%TU) was good (r = 0.820) in group III. The value for %TU in the segments of akinesia was low (35%) and in the those of severe hypokinesia was higher (48%). In all phases, two groups showed significant relationships between %LS and %TU in group I and II. The %TU was unchanged in the akinetic segment, the %LS changed 30% in group I and the %LS changed to 49% in group II. If the %TU is more than 50% (AMI) or 40% (OMI), we would observe viable muscle. The combination of Tl and cardiac pool SPECT are useful for evaluating myocardial viability in the patients with AMI.

[Time consumption and quality of an automated fusion tool for SPECT and MRI images of the brain].

PubMed

Fiedler, E; Platsch, G; Schwarz, A; Schmiedehausen, K; Tomandl, B; Huk, W; Rupprecht, Th; Rahn, N; Kuwert, T

2003-10-01

Although the fusion of images from different modalities may improve diagnostic accuracy, it is rarely used in clinical routine work due to logistic problems. Therefore we evaluated performance and time needed for fusing MRI and SPECT images using a semiautomated dedicated software. PATIENTS, MATERIAL AND METHOD: In 32 patients regional cerebral blood flow was measured using (99m)Tc ethylcystein dimer (ECD) and the three-headed SPECT camera MultiSPECT 3. MRI scans of the brain were performed using either a 0,2 T Open or a 1,5 T Sonata. Twelve of the MRI data sets were acquired using a 3D-T1w MPRAGE sequence, 20 with a 2D acquisition technique and different echo sequences. Image fusion was performed on a Syngo workstation using an entropy minimizing algorithm by an experienced user of the software. The fusion results were classified. We measured the time needed for the automated fusion procedure and in case of need that for manual realignment after automated, but insufficient fusion. The mean time of the automated fusion procedure was 123 s. It was for the 2D significantly shorter than for the 3D MRI datasets. For four of the 2D data sets and two of the 3D data sets an optimal fit was reached using the automated approach. The remaining 26 data sets required manual correction. The sum of the time required for automated fusion and that needed for manual correction averaged 320 s (50-886 s). The fusion of 3D MRI data sets lasted significantly longer than that of the 2D MRI data. The automated fusion tool delivered in 20% an optimal fit, in 80% manual correction was necessary. Nevertheless, each of the 32 SPECT data sets could be merged in less than 15 min with the corresponding MRI data, which seems acceptable for clinical routine use.

Traditional Chinese medicine for the treatment of primary dysmenorrhea: how do Yuanhu painkillers effectively treat dysmenorrhea?

PubMed

Chen, Yuetao; Cao, Yu; Xie, Yanhua; Zhang, Xiaokai; Yang, Qian; Li, Xiaoqian; Sun, Jiyuan; Qiu, Pengcheng; Cao, Wei; Wang, Siwang

2013-09-15

To examine the efficacy of YuanHu painkillers (YHP) as a treatment for primary dysmenorrhea and to reveal YHP's principle formula. A Wistar rat uterine contraction model was utilized in this study. Rats were given 0.698g/kg YHP, 0.07g/kg tetrahydropalmatine (THP; YHP's main component), 0.02g/kg imperatorin (IMP), or THP+IMP (0.07+0.02g/kg) as polypharmacy (PG) by gavage. H&E staining and histopathological examination of the uteri tissue samples were performed. We then detected superoxide dismutase (SOD) and malondialdehyde (MDA), nitric oxide (NO), as well as inducible nitric oxide synthase (iNOS), i-κB, nuclear factor-κB (NF-κB), and cyclooxygenase-2 (COX-2) indices. PG significantly inhibited the uterine contraction of the primary dysmenorrhea rat model (p<0.05), and was significantly different than single-agent therapy (p<0.05). Histopathological examination showed inflammation in the uteri of the control group which YHP and its main constitutes alleviated. THP significantly inhibited the contraction of isolated uteri caused by Ach, PGF2α and oxytocin in a concentration-dependent fashion. THP and IMP both significantly affected the levels of NO, activation of NF-κB, up-regulated the expression of i-κB and down-regulated the expression of both iNOS and COX-2. IMP obviously decreased the level of MDA and increased the activation of SOD (p<0.05). PG obviously improved all the parameters mentioned above (p<0.05). YHP exerted protective effects on primary dysmenorrhea in rats and remarkably alleviated the severity of experimental primary dysmenorrhea. The combined strategy proved to be more effective than either THP or IMP alone and may have synergistic effects in combination in primary dysmenorrhea. Mechanisms that might account for the beneficial effects include abating oxidative stress, inhibiting over-inflammatory reaction, and alleviating the contraction of isolated rat uteri by inhibiting the influx of extracellular Ca(2+). Broad potential for future clinical practice is foreseeable. Copyright © 2013 Elsevier GmbH. All rights reserved.

Radionuclide 131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors

NASA Astrophysics Data System (ADS)

Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

2015-10-01

We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer. Electronic supplementary information (ESI) available: Part of the experimental details and additional experimental results. See DOI: 10.1039/c5nr05585g

CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody therapy of lymphoma patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koral, K.F.; Zasadny, K.R.; Kessler, M.L.

A method of performing {sup 131}I quantitative SPECT imaging is described which uses the superimposition of markers placed on the skin to accomplish fusion of computed tomography (CT) and SPECT image sets. To calculate mean absorbed dose after administration of one of two {sup 131}I-labeled monoclonal antibodies (Mabs), the shape of the time-activity curve is measured by daily diagnostic conjugate views, the y-axis of that curve is normalized by a quantitative SPECT measurement (usually intra-therapy), and the tumor mass is deduced from a concurrent CT volume measurement. The method is applied to six B-cell non-Hodgkin`s lymphoma patients. For four tumorsmore » in three patients treated with the MB1 Mab, a correlation appears to be present between resulting mean absorbed dose and disease response. Including all dosimetric estimates for both antibodies, the range for the specific absorbed dose is within that found by others in treating B-cell lymphoma patients. Excluding a retreated anti-B1 patient, the tumor-specific absorbed dose during anti-B1 therapy is from 1.4 to 1.7 mGy/MBq. For the one anti-B1 patient, where quantitative SPECT and conjugate-view imaging was carried out back to back , the quantitative SPECT-measured activity was somewhat less for the spleen and much less for the tumor than that from conjugate views. The quantitative SPECT plus conjugate views method may be of general utility for macro-dosimetry of {sup 131}If therapies. 18 refs., 3 figs., 5 tabs.« less

Co-registered perfusion SPECT/CT: utility for prediction of improved postoperative outcome in lung volume reduction surgery candidates.

PubMed

Takenaka, Daisuke; Ohno, Yoshiharu; Koyama, Hisanobu; Nogami, Munenobu; Onishi, Yumiko; Matsumoto, Keiko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2010-06-01

To directly compare the capabilities of perfusion scan, SPECT, co-registered SPECT/CT, and quantitatively and qualitatively assessed MDCT (i.e. quantitative CT and qualitative CT) for predicting postoperative clinical outcome for lung volume reduction surgery (LVRS) candidates. Twenty-five consecutive candidates (19 men and six women, age range: 42-72 years) for LVRS underwent preoperative CT and perfusion scan with SPECT. Clinical outcome of LVRS for all subjects was also assessed by determining the difference between pre- and postoperative forced expiratory volume in 1s (FEV(1)) and 6-min walking distance (6MWD). All SPECT examinations were performed on a SPECT scanner, and co-registered to thin-section CT by using commercially available software. On planar imaging, SPECT and SPECT/CT, upper versus lower zone or lobe ratios (U/Ls) were calculated from regional uptakes between upper and lower lung fields in the operated lung. On quantitatively assessed CT, U/L for all subjects was assessed from regional functional lung volumes. On qualitatively assessed CT, planar imaging, SPECT and co-registered SPECT/CT, U/Ls were assessed with a 4-point visual scoring system. To compare capabilities of predicting clinical outcome, each U/L was statistically correlated with the corresponding clinical outcome. Significantly fair or moderate correlations were observed between quantitatively and qualitatively assessed U/Ls obtained with all four methods and clinical outcomes (-0.60

Substorms, Plasmoids, Flux Robes, and Magnetotail Flux Loss on March 25, 1983: CDAW-8

DTIC Science & Technology

1988-10-03

1400 UT. The magnitude and orientation of the 11 GOES 5 OR 1982-01 9A SE14 14 ZSM -l1ORe ISEE 3 -10 -5 5 OReYSM YS m ISEE 1 5 14r- -* IMP 8 0 Fig. lb...and references therein]. ISEE 1 saw a 31% field decrease from 55 nT to 38 nT between 1020 and 1058 UT, and a 35 % decrease from 62 nT to 41 nT between...strength is determined by the component 29 2.5 POLAR CAP AREA 2.0 E ISEE 1 . 5 -i 60 x - 50 IMP 8 - 40 35 ISEE-3 (B = 22nt) 30 25 ISE IMP8 cc" Z u

The Impact of Cognitive Impairment in Dementia on Self-Care Domains in Diabetes Mellitus: A Systematic Search and Narrative Review.

PubMed

Santos, Tamsin; Lovell, Janaka; Shiell, Kerrie; Johnson, Marilyn; Ibrahim, Joseph E

2018-04-29

Self-management is integral to effective chronic disease management. Cognitive impairments (CogImp) associated with dementia have not previously been reviewed in diabetes mellitus (DM) self-care. (i) Whether CogImp associated with dementia impact self-care. (ii) Whether specific CogImp affects key DM self-care processes. A systematic literature search with a narrative review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review examined studies published from January, 2000 to February, 2016 describing the relationship between cognition and DM self-care domains in community dwelling older adults with dementia/CogImp. Eight studies met inclusion criteria. Decrements in all self-care domains were associated with CogImp. Problem solving was related to reduced disease knowledge (OR 0.87, 95% CI=0.49-1.55), resulting in poorer glycemic control. Decision-making impairments manifested as difficulties in adjusting insulin doses, leading to more hospital admissions. People without CogImp were better able to find/utilize resources by adhering to recommended management (OR 1.03, 95% CI=1.02-1.05). A lack of interaction with health care providers was demonstrated through reduced receipt of important routine investigation including eye examinations (ARR=0.85, 95% CI=0.85-0.86), HbA1c testing (ARR=0.96, 95% CI=0.96-0.97) and LDL-C testing (ARR=0.91, 95% CI=0.901-0.914). People without CogImp had better clinic attendance (OR 2.17, 95% CI=1.30-3.70). Action taking deficits were apparent through less self-testing of blood sugar levels (20.2% vs 24.4%, p=0.1) resulting in poorer glycemic control, self-care and more frequent micro/macrovascular complications. Persons with diabetes and CogImp, particularly in domains of learning, memory and executive function, were significantly impaired in all self-care tasks. This article is protected by copyright. All rights reserved.

Limiting concentrations of activated mononucleotides necessary for poly(C)-directed elongation of oligoguanylates

NASA Technical Reports Server (NTRS)

Kanavarioti, A.; Chang, S.; Alberas, D. J.

1990-01-01

Selected imidazolide-activated nucleotides have been subjected to hydrolysis under conditions similar to those that favor their template-directed oligomerization. Rate constants of hydrolysis of the P-N bond in guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) and in guanosine 5'-monophosphate imidazolide (ImpG), kh, have been determined in the presence/absence of magnesium ion as a function of temperature and polycytidylate [poly(C)] concentration. Using the rate constant of hydrolysis of 2-MeImpG and the rate constant of elongation, i.e., the reaction of an oligoguanylate with 2-MeImpG in the presence of poly(C) acting as template, the limiting concentration of 2-MeImpG necessary for oligonucleotide elongation to compete with hydrolysis can be calculated. The limiting concentration is defined as the initial concentration of monomer that results in its equal consumption by hydrolysis and by elongation. These limiting concentrations of 2-MeImpG are found to be 1.7 mM at 37 degrees C and 0.36 mM at 1 degrees C. Boundary conditions in the form of limiting concentration of activated nucleotide may be used to evaluate a prebiotic model for chemical synthesis of biopolymers. For instance, the limiting concentration of monomer can be used as a basis of comparison among catalytic, but nonenzymatic, RNA-type systems. We also determined the rate constant of dimerization of 2-MeImpG, k2 = 0.45 +/- 0.06 M-1 h-1 in the absence of poly(C), and 0.45 +/- 0.06 less than or equal to k2 less than or equal to 0.97 +/- 0.13 M-1 h-1 in its presence at 37 degrees C and pH 7.95.(ABSTRACT TRUNCATED AT 250 WORDS).

Dynamic hydraulic fluid stimulation regulated intramedullary pressure.

PubMed

Hu, Minyi; Serra-Hsu, Frederick; Bethel, Neville; Lin, Liangjun; Ferreri, Suzanne; Cheng, Jiqi; Qin, Yi-Xian

2013-11-01

Physical signals within the bone, i.e. generated from mechanical loading, have the potential to initiate skeletal adaptation. Strong evidence has pointed to bone fluid flow (BFF) as a media between an external load and the bone cells, in which altered velocity and pressure can ultimately initiate the mechanotransduction and the remodeling process within the bone. Load-induced BFF can be altered by factors such as intramedullary pressure (ImP) and/or bone matrix strain, mediating bone adaptation. Previous studies have shown that BFF induced by ImP alone, with minimum bone strain, can initiate bone remodeling. However, identifying induced ImP dynamics and bone strain factor in vivo using a non-invasive method still remains challenging. To apply ImP as a means for alteration of BFF, it was hypothesized that non-invasive dynamic hydraulic stimulation (DHS) can induce local ImP with minimal bone strain to potentially elicit osteogenic adaptive responses via bone-muscle coupling. The goal of this study was to evaluate the immediate effects on local and distant ImP and strain in response to a range of loading frequencies using DHS. Simultaneous femoral and tibial ImP and bone strain values were measured in three 15-month-old female Sprague Dawley rats during DHS loading on the tibia with frequencies of 1Hz to 10Hz. DHS showed noticeable effects on ImP induction in the stimulated tibia in a nonlinear fashion in response to DHS over the range of loading frequencies, where they peaked at 2Hz. DHS at various loading frequencies generated minimal bone strain in the tibiae. Maximal bone strain measured at all loading frequencies was less than 8με. No detectable induction of ImP or bone strain was observed in the femur. This study suggested that oscillatory DHS may regulate the local fluid dynamics with minimal mechanical strain in the bone, which serves critically in bone adaptation. These results clearly implied DHS's potential as an effective, non-invasive intervention for osteopenia and osteoporosis treatments. © 2013. Published by Elsevier Inc. All rights reserved.

Thermal design of the IMP-I and H spacecraft

NASA Technical Reports Server (NTRS)

Hoffman, R. H.

1974-01-01

A description of the thermal subsystem of the IMP-I and H spacecraft is presented. These two spacecraft were of a larger and more advanced type in the Explorer series and were successfully launched in March 1971 and September 1972. The thermal requirements, analysis, and design of each spacecraft are described including several specific designs for individual experiments. Techniques for obtaining varying degrees of thermal isolation and contact are presented. The thermal control coatings including the spaceflight performance of silver-coated FEP Teflon are discussed. Predicted performance is compared to measured flight data. The good agreement between them verifies the validity of the thermal model and the selection of coatings.

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

PubMed Central

Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

2017-01-01

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

Primary postural instability: a cause of recurrent sudden falls in the elderly.

PubMed

Djaldetti, R; Lorberboym, M; Melamed, E

2006-12-01

Elderly patients with recurrent falls are frequently diagnosed with an extrapyramidal syndrome. This study aims to characterise a distinct group of patients with recurrent falls and postural instability as a hallmark of the clinical examination. The study took place in the Movement Disorders Unit, Rabin Medical Center, Petah Tiqva, Israel among 26 patients with recurrent falls who had no clinical evidence of a neurodegenerative disease. Medical records, neurological examination and brain imaging studies were assessed. Falls in these patients were sudden, unprovoked, with no vertigo or loss of consciousness. All had postural instability with minimal or no abnormality on the neurological examination. Brain imaging showed diffuse ischaemic changes in 65%. [(123)I]-FPCIT SPECT with the dopamine transporter ligand, performed in five patients, was normal in all. Recurrent falls might be caused by a neurological syndrome that primarily affects balance control. The importance of identifying this disorder is its distinction from other parkinsonian syndromes causing falls.

Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging.

PubMed

Walker, Katherine L; Judenhofer, Martin S; Cherry, Simon R; Mitchell, Gregory S

2015-01-07

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01-0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatial resolution, linearity, detection limits, and uniformity. With (99m)Tc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system's linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using (99m)Tc MAG-3 and a thyroid scan with (123)I) and one plant study (a (99m)TcO4(-) xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.

Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging

DOE PAGES

Walker, Katherine L.; Judenhofer, Martin S.; Cherry, Simon R.; ...

2014-12-12

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. Furthermore, such high-resolution systems have relatively poor sensitivity (typically 0.01% to 0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatialmore » resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO 4- xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. In conclusion, UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.« less

Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging

NASA Astrophysics Data System (ADS)

Walker, Katherine L.; Judenhofer, Martin S.; Cherry, Simon R.; Mitchell, Gregory S.

2015-01-01

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01-0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatial resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO4- xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.

Fuzzy C-mean clustering on kinetic parameter estimation with generalized linear least square algorithm in SPECT

NASA Astrophysics Data System (ADS)

Choi, Hon-Chit; Wen, Lingfeng; Eberl, Stefan; Feng, Dagan

2006-03-01

Dynamic Single Photon Emission Computed Tomography (SPECT) has the potential to quantitatively estimate physiological parameters by fitting compartment models to the tracer kinetics. The generalized linear least square method (GLLS) is an efficient method to estimate unbiased kinetic parameters and parametric images. However, due to the low sensitivity of SPECT, noisy data can cause voxel-wise parameter estimation by GLLS to fail. Fuzzy C-Mean (FCM) clustering and modified FCM, which also utilizes information from the immediate neighboring voxels, are proposed to improve the voxel-wise parameter estimation of GLLS. Monte Carlo simulations were performed to generate dynamic SPECT data with different noise levels and processed by general and modified FCM clustering. Parametric images were estimated by Logan and Yokoi graphical analysis and GLLS. The influx rate (K I), volume of distribution (V d) were estimated for the cerebellum, thalamus and frontal cortex. Our results show that (1) FCM reduces the bias and improves the reliability of parameter estimates for noisy data, (2) GLLS provides estimates of micro parameters (K I-k 4) as well as macro parameters, such as volume of distribution (Vd) and binding potential (BP I & BP II) and (3) FCM clustering incorporating neighboring voxel information does not improve the parameter estimates, but improves noise in the parametric images. These findings indicated that it is desirable for pre-segmentation with traditional FCM clustering to generate voxel-wise parametric images with GLLS from dynamic SPECT data.

Prognostic evaluation in obese patients using a dedicated multipinhole cadmium-zinc telluride SPECT camera.

PubMed

De Lorenzo, Andrea; Peclat, Thais; Amaral, Ana Carolina; Lima, Ronaldo S L

2016-02-01

The purpose of this study is to evaluate the prognostic value of myocardial perfusion SPECT obtained in CZT cameras (CZT-SPECT) with multipinhole collimation in obese patients. CZT-SPECT may be technically challenging in the obese, and its prognostic value remains largely unknown. Patients underwent single-day, rest/stress (supine and prone) imaging. Images were visually inspected and graded as poor, fair or good/excellent. Summed stress and difference scores (SSS and SDS, respectively) were converted into percentages of total perfusion defect and of ischemic defect by division by the maximum possible score. Obesity was defined as a body mass index (BMI) ≥ 30 kg/m(2) and classified as class I (BMI 30-34.9 kg/m(2)), II (BMI 35-39.9 kg/m(2)), or III (BMI ≥ 40 kg/m(2)). Patients were followed-up by telephone interview for the occurrence of all-cause death, myocardial infarction or revascularization. A Cox proportional hazards analysis was used to assess the independent predictors of death. Among 1396 patients, 365 (26.1 %) were obese (mean BMI 33.9 ± 3.6; 17.5 % class I, 3.4 % class II, and 3.4 % class III). Image quality was good/excellent in 94.5 % of the obese patients. The annualized mortality rates were not significantly different among obese and non-obese patients, being <1 % with normal CZT-SPECT, and increased with the degree of scan abnormality in both obese and non-obese patients. Age, the use of pharmacologic stress and an abnormal CZT-SPECT, but not obesity, were independent predictors of death. In obese patients, single-day rest/stress CZT-SPECT with a multipinhole camera provides prognostic discrimination with high image quality.

Optimization of SPECT-CT Hybrid Imaging Using Iterative Image Reconstruction for Low-Dose CT: A Phantom Study

PubMed Central

Grosser, Oliver S.; Kupitz, Dennis; Ruf, Juri; Czuczwara, Damian; Steffen, Ingo G.; Furth, Christian; Thormann, Markus; Loewenthal, David; Ricke, Jens; Amthauer, Holger

2015-01-01

Background Hybrid imaging combines nuclear medicine imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) with computed tomography (CT). Through this hybrid design, scanned patients accumulate radiation exposure from both applications. Imaging modalities have been the subject of long-term optimization efforts, focusing on diagnostic applications. It was the aim of this study to investigate the influence of an iterative CT image reconstruction algorithm (ASIR) on the image quality of the low-dose CT images. Methodology/Principal Findings Examinations were performed with a SPECT-CT scanner with standardized CT and SPECT-phantom geometries and CT protocols with systematically reduced X-ray tube currents. Analyses included image quality with respect to photon flux. Results were compared to the standard FBP reconstructed images. The general impact of the CT-based attenuation maps used during SPECT reconstruction was examined for two SPECT phantoms. Using ASIR for image reconstructions, image noise was reduced compared to FBP reconstructions for the same X-ray tube current. The Hounsfield unit (HU) values reconstructed by ASIR were correlated to the FBP HU values(R2 ≥ 0.88) and the contrast-to-noise ratio (CNR) was improved by ASIR. However, for a phantom with increased attenuation, the HU values shifted for low X-ray tube currents I ≤ 60 mA (p ≤ 0.04). In addition, the shift of the HU values was observed within the attenuation corrected SPECT images for very low X-ray tube currents (I ≤ 20 mA, p ≤ 0.001). Conclusion/Significance In general, the decrease in X-ray tube current up to 30 mA in combination with ASIR led to a reduction of CT-related radiation exposure without a significant decrease in image quality. PMID:26390216

Morphology supporting function: attenuation correction for SPECT/CT, PET/CT, and PET/MR imaging

PubMed Central

Lee, Tzu C.; Alessio, Adam M.; Miyaoka, Robert M.; Kinahan, Paul E.

2017-01-01

Both SPECT, and in particular PET, are unique in medical imaging for their high sensitivity and direct link to a physical quantity, i.e. radiotracer concentration. This gives PET and SPECT imaging unique capabilities for accurately monitoring disease activity for the purposes of clinical management or therapy development. However, to achieve a direct quantitative connection between the underlying radiotracer concentration and the reconstructed image values several confounding physical effects have to be estimated, notably photon attenuation and scatter. With the advent of dual-modality SPECT/CT, PET/CT, and PET/MR scanners, the complementary CT or MR image data can enable these corrections, although there are unique challenges for each combination. This review covers the basic physics underlying photon attenuation and scatter and summarizes technical considerations for multimodal imaging with regard to PET and SPECT quantification and methods to address the challenges for each multimodal combination. PMID:26576737

GATE simulation of a new design of pinhole SPECT system for small animal brain imaging

NASA Astrophysics Data System (ADS)

Uzun Ozsahin, D.; Bläckberg, L.; El Fakhri, G.; Sabet, H.

2017-01-01

Small animal SPECT imaging has gained an increased interest over the past decade since it is an excellent tool for developing new drugs and tracers. Therefore, there is a huge effort on the development of cost-effective SPECT detectors with high capabilities. The aim of this study is to simulate the performance characteristics of new designs for a cost effective, stationary SPECT system dedicated to small animal imaging with a focus on mice brain. The conceptual design of this SPECT system platform, Stationary Small Animal SSA-SPECT, is to use many pixelated CsI:TI detector modules with 0.4 mm × 0.4 mm pixels in order to achieve excellent intrinsic detector resolution where each module is backed by a single pinhole collimator with 0.3 mm hole diameter. In this work, we present the simulation results of four variations of the SSA-SPECT platform where the number of detector modules and FOV size is varied while keeping the detector size and collimator hole size constant. Using the NEMA NU-4 protocol, we performed spatial resolution, sensitivity, image quality simulations followed by a Derenzo-like phantom evaluation. The results suggest that all four SSA-SPECT systems can provide better than 0.063% system sensitivity and < 1.5 mm FWHM spatial resolution without resolution recovery or other correction techniques. Specifically, SSA-SPECT-1 showed a system sensitivity of 0.09% in combination with 1.1 mm FWHM spatial resolution.

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Cyclotron laboratory of the Institute for Nuclear Research and Nuclear Energy

NASA Astrophysics Data System (ADS)

Tonev, D.; Goutev, N.; Georgiev, L. S.

2016-06-01

An accelerator laboratory is presently under construction in Sofia at the Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences. The laboratory will use a TR24 type of cyclotron, which provides a possibility to accelerate a proton beam with an energy of 15 to 24 MeV and current of up to 0.4 mA. An accelerator with such parameters allows to produce a large variety of radioisotopes for development of radiopharmaceuticals. The most common radioisotopes that could be produced with such a cyclotron are PET isotopes like: 11C, 13N, 15O, 18F, 124I, 64Cu, 68Ge/68Ga, and SPECT isotopes like: 123I, 111In, 67Ga, 57Co, 99m Tc. Our aim is to use the cyclotron facility for research in the fields of radiopharmacy, radiochemistry, radiobiology, nuclear physics, solid state physics, applied research, new materials and for education in all these fields including nuclear energy. The building of the laboratory will be constructed nearby the Institute for Nuclear Research and Nuclear Energy and the cyclotron together with all the equipment needed will be installed there.

SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone.

PubMed

Sharma, Punit; Sharma, Shekhar; Ballal, Sanjana; Bal, Chandrasekhar; Malhotra, Arun; Kumar, Rakesh

2012-09-01

To assess the patient radiation dose during routine clinical single-photon emission computed tomography-computed tomography (SPECT-CT) and measure the increase as compared with SPECT alone. Data pertaining to 357 consecutive patients who had undergone radioisotope imaging along with SPECT-CT of a selected volume were retrospectively evaluated. Dose of the injected radiopharmaceutical (MBq) was noted, and the effective dose (mSv) was calculated as per International Commission on Radiological Protection (ICRP) guidelines. The volume-weighted computed tomography dose index (CTDIvol) and dose length product of the CT were also assessed using standard phantoms. The effective dose (mSv) due to CT was calculated as the product of dose length product and a conversion factor depending on the region of investigation, using ICRP guidelines. The dose due to CT was compared among different investigations. The increase in effective dose was calculated as CT dose expressed as a percentage of radiopharmaceutical dose. The per-patient CT effective dose for different studies varied between 0.06 and 11.9 mSv. The mean CT effective dose was lowest for 99mTc-ethylene cysteine dimer brain SPECT-CT (0.9 ± 0.7) and highest for 99mTc-methylene diphosphonate bone SPECT-CT (4.2 ± 2.8). The increase in radiation dose (SPECT-CT vs. SPECT) varied widely (2.3-666.4% for 99mTc-tracers and 0.02-96.2% for 131I-tracers). However, the effective dose of CT in SPECT-CT was less than the values reported for conventional CT examinations of the same regions. Addition of CT to nuclear medicine imaging in the form of SPECT-CT increases the radiation dose to the patient, with the effective dose due to CT exceeding the effective dose of RP in many instances. Hence, appropriate utilization and optimization of the protocols of SPECT-CT is needed to maximize benefit to patients.

SPECT in patients with cortical visual loss.

PubMed

Silverman, I E; Galetta, S L; Gray, L G; Moster, M; Atlas, S W; Maurer, A H; Alavi, A

1993-09-01

Single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was used to investigate changes in cerebral blood flow in seven patients with cortical visual impairment. Traumatic brain injury (TBI) was the cause of cortical damage in two patients, cerebral ischemia in two patients and carbon monoxide (CO) poisoning, status epilepticus and Alzheimer's Disease (AD) each in three separate patients. The SPECT scans of the seven patients were compared to T2-weighted magnetic resonance image (MRI) scans of the brain to determine the correlation between functional and anatomical findings. In six of the seven patients, the qualitative interpretation of the SPECT studies supported the clinical findings (i.e., the visual field defect) by revealing altered regional cerebral blood flow (rCBF) in the appropriate regions of the visual pathway. MR scans in all of the patients, on the other hand, were either normal or disclosed smaller lesions than those detected by SPECT. We conclude that SPECT may reveal altered rCBF in patients with cortical visual impairment of various etiologies, even when MRI studies are normal or nondiagnostic.

Oncofetal protein IMP3, a new cancer biomarker.

PubMed

Gong, Yuna; Woda, Bruce A; Jiang, Zhong

2014-05-01

IMP3 is a member of a family of RNA-binding proteins that consists of IMP1, IMP2 and IMP3. These proteins contain 2 RNA recognition motifs and 4 K-homology domains that allow them to bind RNAs strongly and specifically. IMP3 is an oncofetal protein involved in embryogenesis and its expression is associated with a number of malignant neoplasms. IMP3 is associated with aggressive and advanced cancers and is specifically expressed in malignant tumors but is not found in adjacent benign tissues. Moreover, in vitro studies have shown that IMP3 promotes tumor cell proliferation, adhesion, and invasion. This review focuses on the studies of IMP3 expression in different cancers and emphasizes the potential utility of IMP3 in routine surgical pathology practice. We also discuss IMP3 as a prognostic biomarker for cancer patients' outcomes.

Solar bus regulator and battery charger for IMP's H, I, and J

NASA Technical Reports Server (NTRS)

Paulkovich, J.

1972-01-01

Interplanetary Monitoring Probe (IMP) spacecrafts H, I, and J utilize a direct energy transfer (DET) type of power system operating from a solar array source. A shunt type of regulator prevents the bus voltage from exceeding a preset voltage level. The power system utilizes a single differential amplifier with dual outputs to control the battery charge/shunt regulator and the discharge regulator. A two-voltage level, current limited, series charger and a current sensor control battery state of charge of the silver-cadmium battery pack. Premature termination of the battery charge is prevented by a power available gate that also initiates charge current to the battery upon availability of excess power.

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Current activities in the ICRP concerning estimation of radiation doses to patients from radiopharmaceuticals for diagnostic use

NASA Astrophysics Data System (ADS)

Mattsson, S.; Johansson, L.; Leide-Svegborn, S.; Liniecki, J.; Nosske, D.; Riklund, K.; Stabin, M.; Taylor, D.

2011-09-01

A Task Group within the ICRP Committees 2 and 3 is continuously working to improve absorbed dose estimates to patients investigated with radiopharmaceuticals. The work deals with reviews of the literature, initiation of new or complementary studies of the biokinetics of a compound and dose estimates. Absorbed dose calculations for organs and tissues have up to now been carried out using the MIRD formalism. There is still a lack of necessary biokinetic data from measurements in humans. More time series obtained by nuclear medicine imaging techniques such as whole-body planar gamma-camera imaging, SPECT or PET are highly desirable for this purpose. In 2008, a new addendum to ICRP Publication 53 was published under the name of ICRP Publication 106 containing biokinetic data and absorbed dose information to organs and tissues of patients of various ages for radiopharmaceuticals in common use. That report also covers a number of generic models and realistic maximum models covering other large groups of substances (e.g. "123I-brain receptor substances"). Together with ICRP Publication 80, most radiopharmaceuticals in clinical use at the time of publication were covered except the radioiodine labeled compounds for which the ICRP dose estimates are still found in Publication 53. There is an increasing use of new radiopharmaceuticals, especially PET-tracers and the TG has recently finished its work with biokinetic and dosimetric data for 18F-FET, 18F-FLT and 18F-choline. The work continues now with new data for 11C-raclopride, 11C-PiB and 123I-ioflupan as well as re-evaluation of published data for 82Rb-chloride, 18F-fluoride and radioiodide. This paper summarises published ICRP-information on dose to patients from radiopharmaceuticals and gives some preliminary data for substances under review.

DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

PubMed

Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2013-01-01

The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

DRD2 Genotype-Based Variation of Default Mode Network Activity and of Its Relationship With Striatal DAT Binding

PubMed Central

Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2013-01-01

The default mode network (DMN) comprises a set of brain regions with “increased” activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([123I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling. PMID:21976709

Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

PubMed Central

Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

2015-01-01

One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D2/3 receptor binding potential (BPp) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [123I]iodobenzamide ([123I]-IBZM) was used to examine striatal D2/3 receptor BPp. Patients were examined before and after 6 weeks of treatment with the D2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D2/3 receptor BPp at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BPp in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BPp of dopamine D2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BPp have a better treatment response than patients with a high BPp. The results further suggest that functioning may decline at high levels of dopamine receptor blockade. PMID:25698711

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

PubMed

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell and gene therapy and is conducted at a high level of pharmaceutical quality ensuring patient safety. This patient-tailored approach represents the first clinical study worldwide utilizing genetically engineered MSCs in humans. EU Clinical Trials Register/European Union Drug Regulating Authorities Clinical Trials Database number: 2012-003741-15.

IMP-29, a Novel IMP-Type Metallo-β-Lactamase in Pseudomonas aeruginosa

PubMed Central

Jeannot, Katy; Poirel, Laurent; Robert-Nicoud, Marjorie; Cholley, Pascal; Nordmann, Patrice

2012-01-01

Analysis of two clonally related multiresistant Pseudomonas aeruginosa isolates led to the identification of a novel IMP-type metallo-β-lactamase. IMP-29 was significantly different from the other IMP variants (the closest variant being IMP-5 with 93% amino acid identity). The blaIMP-29 gene cassette was carried by a class 1 integron in strain 10.298, while in strain 10.266 it was located in a rearranged DNA region on a 30-kb conjugative plasmid. Biochemical analysis confirmed that IMP-29 efficiently hydrolyzed carbapenems. PMID:22290960

IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma.

PubMed

Gao, Yuanyuan; Yang, Michelle; Jiang, Zhong; Woda, Bruce A; Mercurio, Arthur M; Qin, Jianjie; Huang, Xinli; Zhang, Feng

2014-06-01

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer. Copyright © 2014 The Auhtors. Published by Elsevier Inc. All rights reserved.

IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1 mRNA and Other mRNAs encoding mitochondrial proteins.

PubMed

Dai, Ning; Zhao, Liping; Wrighting, Diedra; Krämer, Dana; Majithia, Amit; Wang, Yanqun; Cracan, Valentin; Borges-Rivera, Diego; Mootha, Vamsi K; Nahrendorf, Matthias; Thorburn, David R; Minichiello, Liliana; Altshuler, David; Avruch, Joseph

2015-04-07

Although variants in the IGF2BP2/IMP2 gene confer risk for type 2 diabetes, IMP2, an RNA binding protein, is not known to regulate metabolism. Imp2(-/-) mice gain less lean mass after weaning and have increased lifespan. Imp2(-/-) mice are highly resistant to diet-induced obesity and fatty liver and display superior glucose tolerance and insulin sensitivity, increased energy expenditure, and better defense of core temperature on cold exposure. Imp2(-/-) brown fat and Imp2(-/-) brown adipocytes differentiated in vitro contain more UCP1 polypeptide than Imp2(+/+) despite similar levels of Ucp1 mRNA; the Imp2(-/-)adipocytes also exhibit greater uncoupled oxygen consumption. IMP2 binds the mRNAs encoding Ucp1 and other mitochondrial components, and most exhibit increased translational efficiency in the absence of IMP2. In vitro IMP2 inhibits translation of mRNAs bearing the Ucp1 untranslated segments. Thus IMP2 limits longevity and regulates nutrient and energy metabolism in the mouse by controlling the translation of its client mRNAs. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

PubMed Central

Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count.

PubMed

Mizumura, Sunao; Nishikawa, Kazuhiro; Murata, Akihiro; Yoshimura, Kosei; Ishii, Nobutomo; Kokubo, Tadashi; Morooka, Miyako; Kajiyama, Akiko; Terahara, Atsuro

2018-05-01

In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123 I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic procedures.

PubMed

Audenaert, Kurt; Jansen, Hugo M L; Otte, Andreas; Peremans, Kathelijne; Vervaet, Myriam; Crombez, Roger; de Ridder, Leo; van Heeringen, Cees; Thirot, Joel; Dierckx, Rudi; Korf, Jaap

2003-10-01

Traumatic brain injury (TBI) is usually assessed with the Glasgow Coma Scale (GCS), CT and EEG. TBI can result from either the primary mechanical impact or secondary (ischemic) brain damage, in which calcium (Ca) plays a pivotal role. This study was undertaken to compare the applicability of SPECT using 57Co as a Ca-tracer in patients with mild traumatic brain injury. 8 patients with mild TBI (GCS 15) were clinically examined and studied with EEG, neuropsychological testing (NPT) and SPECT within 2 days post-TBI. After i.v.-administration of 37 MBq (1 mCi) 57Co (effective radiation dose 0.34 mSv x MBq(-1); 1.24 rem x mCi(-1); physical half-life 270 days, biological half-life 37.6 h), single-headed SPECT (12 h pi) was performed, consecutively followed by standard 925 MBq (25 mCi) Tc-99m HMPAO SPECT. In 6 of the 8 patients, baseline NPT and SPECT showed focal abnormalities in the affected frontal and temporal brain regions, which were in good topographical accordance. CT and EEG did not detect (structural) lesions in any of these cases. Single-headed 57Co-SPECT is able to show the site and extent of brain damage in patients with mild TBI, even in the absence of structural lesions. It may confirm and localize NPT findings. The predictive value of 57Co-SPECT should be assessed in larger patient series.

[Transient charles bonnet syndrome after excision of a right occipital meningioma: a case report].

PubMed

Arai, Takao; Hasegawa, Yuzuru; Tanaka, Toshihide; Kato, Naoki; Watanabe, Mitsuyoshi; Nakamura, Aya; Murayama, Yuichi

2014-05-01

Charles Bonnet syndrome is a condition characterized by visual hallucinations. These simple or complex visual hallucinations are more common in elderly individuals with impaired peripheral vision. The current report describes a case of transient Charles Bonnet syndrome appearing after the removal of a meningioma. The patient was a 61-year-old man who already had impaired visual acuity due to diabetic retinopathy. Brain MRI revealed a cystic tumor severely compressing the right occipital lobe. Starting on day 2 postoperatively, the patient was troubled by recurring visual hallucinations involving people, flowers, pictures, and familiar settings(the train and a coffee shop). These continued for 3.5 months. This period roughly coincided with the time for the occipital lobe to recover from the compression caused by the tumor, a fact that was confirmed by several MRI scans. ¹²³I-IMP SPECT performed 1 month after the surgical operation showed an area of hypoperfusion in the right parieto-occipital lobe. Based on the patient's clinical course and MRI findings, the mechanism of onset of visual hallucinations in this patient was put forward. The release of pressure in the brain by tumor removal and subsequent recovery changed the blood flow to the brain. This triggered visual hallucinations in the patient, who was already predisposed to developing Charles Bonnet syndrome because of diabetic retinopathy. This case is interesting since it indicates that central neurological factors, as well as visual deficits, may induce the appearance of visual hallucinations in Charles Bonnet syndrome.

Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae.

PubMed

Matsumura, Yasufumi; Peirano, Gisele; Motyl, Mary R; Adams, Mark D; Chen, Liang; Kreiswirth, Barry; DeVinney, Rebekah; Pitout, Johann D D

2017-04-01

International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific bla IMP -containing integrons (In809 with bla IMP-4 , In722 with bla IMP-6 , and In687 with bla IMP-14 ) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with bla IMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae ( n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with bla IMP-26 and In1321 with bla IMP-6 The Enterobacter cloacae complex ( n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with bla IMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with bla IMP genes. Copyright © 2017 American Society for Microbiology.

Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae

PubMed Central

Peirano, Gisele; Motyl, Mary R.; Adams, Mark D.; Chen, Liang; Kreiswirth, Barry; DeVinney, Rebekah

2017-01-01

ABSTRACT International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific blaIMP-containing integrons (In809 with blaIMP-4, In722 with blaIMP-6, and In687 with blaIMP-14) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with blaIMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae (n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with blaIMP-26 and In1321 with blaIMP-6. The Enterobacter cloacae complex (n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with blaIMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with blaIMP genes. PMID:28167555

Molecular analysis of the integrons of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates collected by nationwide surveillance programs across Japan.

PubMed

Mano, Yoko; Saga, Tomoo; Ishii, Yoshikazu; Yoshizumi, Ayumi; Bonomo, Robert A; Yamaguchi, Keizo; Tateda, Kazuhiro

2015-02-21

We investigate the evolving molecular epidemiology of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates collected in a 100 institution, nationwide surveillance study in Japan from 2004 to 2006. MBL-producers were detected in 23/996 isolates (2.3%) in 2004 and 21/992 (2.1%) in 2006. Antimicrobial resistance (specifically, carbapenem resistance) rates between two periods did not differ significantly. MBL-producers were more prevalent in urinary tract isolates. bla IMP-1 group was the most predominant (38 isolates, 80%), followed by 3 bla IMP-7, 2 bla IMP-11 group, and 1 bla VIM-1. All MBL genes were identified in 16 different class 1 integrons, most of which were novel to INTEGRALL database. A total of 17 isolates of sequence type (ST) 235, a recognized worldwide drug-resistant lineage, were distributed in 5 geographic regions across Japan. ST235 isolates included a sublineage associated with In113-like integron. ST357 was identified in 14 isolates, 9 of which harboring a sole bla IMP-1 gene cassette (In994) were recovered from Chugoku region in 2004. ST357 isolates with bla IMP-11 group or ST235 with bla IMP-7 emerged in 2006. We also report for the first time the presence of novel fosI gene cassette in strains other than Mycobacterium spp. Our data give an important "snapshot" of the molecular characteristics and dynamics of MBL-producing lineages in P. aeruginosa in Japan. The significant association of specific genotypes and integrons implies that dissemination and transmission of the preexisting resistant lineage, rather than horizontal gene transfer in situ, might largely explain their endemicity.

Identification of urinary metabolites of imperatorin with a single run on an LC/Triple TOF system based on multiple mass defect filter data acquisition and multiple data mining techniques.

PubMed

Qiao, Shi; Shi, Xiaowei; Shi, Rui; Liu, Man; Liu, Ting; Zhang, Kerong; Wang, Qiao; Yao, Meicun; Zhang, Lantong

2013-08-01

The detection of drug metabolites, especially for minor metabolites, continues to be a challenge because of the complexity of biological samples. Imperatorin (IMP) is an active natural furocoumarin component originating from many traditional Chinese herbal medicines and is expected to be pursued as a new vasorelaxant agent. In the present study, a generic and efficient approach was developed for the in vivo screening and identification of IMP metabolites using liquid chromatography-Triple TOF mass spectrometry. In this approach, a novel on-line data acquisition method mutiple mass defect filter (MMDF) combined with dynamic background subtraction was developed to trace all probable urinary metabolites of IMP. Comparing with the traditionally intensity-dependent data acquisition method, MMDF method could give the information of low-level metabolites masked by background noise and endogenous components. Thus, the minor metabolites in complex biological matrices could be detected. Then, the sensitive and specific multiple data-mining techniques extracted ion chromatography, mass defect filter, product ion filter, and neutral loss filter were used for the discovery of IMP metabolites. Based on the proposed strategy, 44 phase I and 7 phase II metabolites were identified in rat urine after oral administration of IMP. The results indicated that oxidization was the main metabolic pathway and that different oxidized substituent positions had a significant influence on the fragmentation of the metabolites. Two types of characteristic ions at m/z 203 and 219 can be observed in the MS/MS spectra. This is the first study of IMP metabolism in vivo. The interpretation of the MS/MS spectra of these metabolites and the proposed metabolite pathway provide essential data for further pharmacological studies of other linear-type furocoumarins.

Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre-clinical tomograph

NASA Astrophysics Data System (ADS)

Spinks, T. J.; Karia, D.; Leach, M. O.; Flux, G.

2014-02-01

The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems and thus provides a range of pre-clinical imaging options. The PET component consists of three rings of single-crystal LYSO detectors with axial/transverse fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI detectors (100 × 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH) collimators; the detectors rotate in 6° increments and their spacing can be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides ‘low’ (200 µA, 35 kVp) or ‘high’ (400 µA, 45 kVp) power x-rays onto a flat-panel CsI detector. This study examines the performance characteristics and quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008 specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable activity range is ≤ 10 MBq (18F) over which good linearity (within 5%) is obtained for a uniform cylinder spanning the axial FOV; increasing deviation from linearity with activity is, however, observed for the NEMA (mouse) line source phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point source sensitivity 69/750 cps MBq-1. Axial uniformity of SPECT images (%CV of regions-of-interest counts along the axis) is mostly within 8% although there is a range of 30-40% for the largest FOV. The variation is significantly smaller within the central 40 mm. Instances of count rate nonlinearity (PET) and axial non-uniformity (SPECT) were found to be reproducible and thus amenable to empirical correction.

D- and L-[123I]-2-I-phenylalanine show a long tumour retention compared with D- and L-[123I]-2-I-tyrosine in R1M rhabdomyosarcoma tumour-bearing Wag/Rij rats.

PubMed

Bauwens, Matthias; Lahoutte, Tony; Kersemans, Ken; Caveliers, Vicky; Bossuyt, Axel; Mertens, John

2007-07-01

The aim of this study was the comparison of the tumour uptake and the long-term retention of [(123)I]-2-I-L-phenylalanine and [(123)I]-2-I-D-phenylalanine with those of [(123)I]-2-I-L-tyrosine and [(123)I]-2-I-D-tyrosine in R1M rhabdomyosarcoma tumour-bearing rats. The biodistribution of the radioactivity as a function of time in R1M tumour-bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting. [(123)I]-2-iodo-L-phenylalanine, [(123)I]-2-iodo-D-phenylalaine, [(123)I]-2-I-L-tyrosine showed a considerable tumour uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L- and D- [(123)I]-2-I-tyrosine were cleared for a large part from the tumours and the body. [(123)I]-2-I-L-Phe and [(123)I]-2-I-D-Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour-to-background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the R1M-bearing Wag/Rij rat model only [(123)I]-2-I-L-phenylalanine and [(123)I]-2-I-D-phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers. Copyright 2007 John Wiley & Sons, Ltd.

Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

PubMed

de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

2016-01-01

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer by 99mTc-MIBI SPECT/CT; a pilot study.

PubMed

Tangjaturonrasme, Napadon; Vasavid, Pataramon; Sombuntham, Premsuda; Keelawat, Somboon

2013-06-01

Papillary thyroid cancer has a high prevalence of cervical nodal metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary thyroid cancer Fifteen patients were performed 99Tc-MlBI SPECT/CT pre-operatively. Either positive pathological report of neck dissection or positive post-treatment I-131 whole body scan with SPECT/CT of neck was concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI SPECT/CT were analyzed. The PPV NPV and accuracy were 80%, 88.89%, and 85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes groups correctly in most cases when compared with pathological results. However the authors found one false positive case with caseating granulomatous lymphadenitis and one false negative case with positive post-treatment 1-131 whole body scan with SPECT/CT of neck on cervical nodes zone II and IV CONCLUSION: 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of cervical nodal involvement in patients with papillary thyroid cancer without the need of using iodinated contrast that may complicate subsequence 1-131 treatment. However, false positive result in granulomatous inflammatory nodes should be aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good result when compared with previous study of CT or MRI imaging. The comparative study between different imaging modality and the extension of neck dissection according to MIBI result seems interesting.

Optimized 3D stitching algorithm for whole body SPECT based on transition error minimization (TEM)

NASA Astrophysics Data System (ADS)

Cao, Xinhua; Xu, Xiaoyin; Voss, Stephan

2017-02-01

Standard Single Photon Emission Computed Tomography (SPECT) has a limited field of view (FOV) and cannot provide a 3D image of an entire long whole body SPECT. To produce a 3D whole body SPECT image, two to five overlapped SPECT FOVs from head to foot are acquired and assembled using image stitching. Most commercial software from medical imaging manufacturers applies a direct mid-slice stitching method to avoid blurring or ghosting from 3D image blending. Due to intensity changes across the middle slice of overlapped images, direct mid-slice stitching often produces visible seams in the coronal and sagittal views and maximal intensity projection (MIP). In this study, we proposed an optimized algorithm to reduce the visibility of stitching edges. The new algorithm computed, based on transition error minimization (TEM), a 3D stitching interface between two overlapped 3D SPECT images. To test the suggested algorithm, four studies of 2-FOV whole body SPECT were used and included two different reconstruction methods (filtered back projection (FBP) and ordered subset expectation maximization (OSEM)) as well as two different radiopharmaceuticals (Tc-99m MDP for bone metastases and I-131 MIBG for neuroblastoma tumors). Relative transition errors of stitched whole body SPECT using mid-slice stitching and the TEM-based algorithm were measured for objective evaluation. Preliminary experiments showed that the new algorithm reduced the visibility of the stitching interface in the coronal, sagittal, and MIP views. Average relative transition errors were reduced from 56.7% of mid-slice stitching to 11.7% of TEM-based stitching. The proposed algorithm also avoids blurring artifacts by preserving the noise properties of the original SPECT images.

Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients

PubMed Central

Bouwmans, Angela E P; Vlaar, Annemarie M M; Mess, Werner H; Kessels, Alfons; Weber, Wim E J

2013-01-01

Objective Numerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated. Design Prospective cohort study for diagnostic accuracy. Setting Neurology outpatient clinics of two teaching hospitals in the Netherlands. Patients 196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a 123I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176). Outcome measures After 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study. Results Temporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84. Conclusions The diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use. Clinicaltrials.gov identifier NCT0036819 PMID:23550093

Energetic particle flux experiment (IMP-F and G)

NASA Technical Reports Server (NTRS)

Anderson, K. A.

1972-01-01

The technical aspects of the University of California IMP-F experiment aboard the Explorer-34 and the University of California IMP-G (S1) and (S2) experiments aboard the Explorer-41. The experiment detectors and electronics are discussed for each experiment as well as the fabrication, preflight and post-flight history. A description of the ground support equipment is also given for each experiment. These three experiments were essentially all different. The IMP-G experiment was essentially the IMP-F experiment with the addition of four Geiger-Mueller detectors. The IMP-G (S-2) was a supplementary experiment and differed completely from the IMP-F and IMP-G experiments. It was concluded that the ground support equipment approach used for the IMP-F and IMP-G experiments where emphasis was placed on a thorough exercise and monitoring of the experiment operation during various testing phases provided a high degree of confidence and reliability in these experiments. No known electronic failures have occurred during the spacecraft lifetime although some detector problems were experienced.

Cyclotron production of I-123: An evaluation of the nuclear reactions which produce this isotope

NASA Technical Reports Server (NTRS)

Sodd, V. J.; Scholz, K. L.; Blue, J. W.; Wellman, H. N.

1970-01-01

The use of the various nuclear reactions is described by which I-123,a low radiation dose radiopharmaceutical, can be cyclotron-produced. Methods of directly producing I-123 and those which indirectly produce the radionuclide through the beta (+) decay of its nautral precursor, Xe-123. It is impossible to separate from the radioiodine contaminants, notably I-124, which occur in the direct method. Thus, it is preferable to produce pure I-123 from Xe-123 which is easily separated from the radioiodines. Among the characteristics of I-123 is the capability of reducing the patient dose in a thyroid uptake measurement to a very small percentage of that delivered by the more commonly used I-131.

Machine-learning model observer for detection and localization tasks in clinical SPECT-MPI

NASA Astrophysics Data System (ADS)

Parages, Felipe M.; O'Connor, J. Michael; Pretorius, P. Hendrik; Brankov, Jovan G.

2016-03-01

In this work we propose a machine-learning MO based on Naive-Bayes classification (NB-MO) for the diagnostic tasks of detection, localization and assessment of perfusion defects in clinical SPECT Myocardial Perfusion Imaging (MPI), with the goal of evaluating several image reconstruction methods used in clinical practice. NB-MO uses image features extracted from polar-maps in order to predict lesion detection, localization and severity scores given by human readers in a series of 3D SPECT-MPI. The population used to tune (i.e. train) the NB-MO consisted of simulated SPECT-MPI cases - divided into normals or with lesions in variable sizes and locations - reconstructed using filtered backprojection (FBP) method. An ensemble of five human specialists (physicians) read a subset of simulated reconstructed images, and assigned a perfusion score for each region of the left-ventricle (LV). Polar-maps generated from the simulated volumes along with their corresponding human scores were used to train five NB-MOs (one per human reader), which are subsequently applied (i.e. tested) on three sets of clinical SPECT-MPI polar maps, in order to predict human detection and localization scores. The clinical "testing" population comprises healthy individuals and patients suffering from coronary artery disease (CAD) in three possible regions, namely: LAD, LcX and RCA. Each clinical case was reconstructed using three reconstruction strategies, namely: FBP with no SC (i.e. scatter compensation), OSEM with Triple Energy Window (TEW) SC method, and OSEM with Effective Source Scatter Estimation (ESSE) SC. Alternative Free-Response (AFROC) analysis of perfusion scores shows that NB-MO predicts a higher human performance for scatter-compensated reconstructions, in agreement with what has been reported in published literature. These results suggest that NB-MO has good potential to generalize well to reconstruction methods not used during training, even for reasonably dissimilar datasets (i.e. simulated vs. clinical).

Molecular and epidemiological characterization of IMP-type metallo-β-lactamase-producing Enterobacter cloacae in a Large tertiary care hospital in Japan.

PubMed

Hayakawa, Kayoko; Miyoshi-Akiyama, Tohru; Kirikae, Teruo; Nagamatsu, Maki; Shimada, Kayo; Mezaki, Kazuhisa; Sugiki, Yuko; Kuroda, Emi; Kubota, Shiho; Takeshita, Nozomi; Kutsuna, Satoshi; Tojo, Masayoshi; Ohmagari, Norio

2014-06-01

IMP-type metallo-β-lactamase enzymes have been reported in different geographical areas and in various Gram-negative bacteria. However, the risk factors and epidemiology pertaining to IMP-type metallo-β-lactamase-producing Enterobacter cloacae (IMP-producing E. cloacae) have not been systematically evaluated. We conducted a retrospective, matched case-control study of patients from whom IMP-producing E. cloacae isolates were obtained, in addition to performing thorough molecular analyses of the clinically obtained IMP-producing E. cloacae isolates. Unique cases with IMP-producing E. cloacae isolation were included. Patients with IMP-producing E. cloacae were matched to uninfected controls at a ratio of 1 to 3. Fifteen IMP-producing E. cloacae cases were identified, with five of the isolates being obtained from blood, and they were matched to 45 uninfected controls. All (100%) patients from whom IMP-producing E. cloacae isolates were obtained had indwelling devices at the time of isolation, compared with one (2.2%) uninfected control. Independent predictors for isolation of IMP-producing E. cloacae were identified as cephalosporin exposure and invasive procedures within 3 months. Although in-hospital mortality rates were similar between cases and controls (14.3% versus 13.3%), the in-hospital mortality of patients with IMP-producing E. cloacae-caused bacteremia was significantly higher (40%) than the rate in controls. IMP-producing E. cloacae isolates were frequently positive for other resistance determinants. The MICs of meropenem and imipenem were not elevated; 10 (67%) and 12 (80%) of the 15 IMP-producing E. cloacae isolates had a MIC of ≤ 1 μg/ml. A phylogenetic tree showed a close relationship among the IMP-producing E. cloacae samples. Indwelling devices, exposure to cephalosporin, and a history of invasive procedures were associated with isolation of IMP-producing E. cloacae. Screening for carbapenemase production is important in order to apply appropriate clinical management and infection control measures. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: A female twin study

PubMed Central

Knopik, Valerie S.; Heath, Andrew C.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Waldron, Mary

2009-01-01

Genetic and environmental contributions to the observed correlations among DSM-IV ADHD problems [inattentive (INATT) and hyperactive/impulsive (HYP/IMP) behaviors], conduct problems (CDP) and alcohol problems (AlcProb) were examined by fitting multivariate structural equation models to data from the Missouri Adolescent Female Twin Study [N=2892 twins (831 monozygotic pairs, 615 dizygotic pairs)]. Based on results of preliminary regression models, we modified the structural model to jointly estimate (i) the regression of each phenotype on significant familial/prenatal predictors, and (ii) genetic and environmental contributions to the residual variance and covariance. Results suggested that (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports, genetic effects on alcohol dependence symptoms were negligible; and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb), a finding that could inform different approaches to treatment and prevention. PMID:19341765

IMPROVED EQUIPMENT CLEANING IN COATED AND LAMINATED SUBSTRATE MANUFACTURING FACILITIES (PHASE I)

EPA Science Inventory

The report gives results of a Phase I study to characterize current equipment cleaning practices in the coated and laminated substrate manufacturing industry, to identify alternative cleaning technologies, and to identify demonstrable technologies and estimate their emissions imp...

Use of molecular targeted agents for the diagnosis, staging and therapy of neuroendocrine malignancy

PubMed Central

2010-01-01

Abstract Imaging of neuroendocrine tumours (NET) poses significant challenges because of the heterogeneous biology of the tumours that are represented by this class of neoplasia. NET can range from benign lesions to highly aggressive cancers. Structural imaging techniques have suboptimal sensitivity in most published series and diagnosis is often delayed until metastatic disease is present. Current guidelines emphasise the importance of functional imaging for evaluating the extent of NET. The mainstay of this type of imaging has been somatostatin receptor scintigraphy (SRS) with [111In]diethylenetriaminepentaacetic acid-octreotide (Octreoscan™). Routine use of single-photon emission computed tomography (SPECT) and particularly of hybrid SPECT/computed tomography (CT) has significantly improved localisation of tumour sites and evaluation of somatostatin receptor (SSTR) expression, which is important for predicting the likelihood of response to somatostatin analogues (SSA). Positron emission tomography (PET) can also now be used for evaluating SSTR expression. There are a number of peptides that have been evaluated but [68Ga]tetraazocyclodecanetetraacetic acid (DOTA)-octreotate (GaTate) PET/CT, which has been shown to be significantly more sensitive for detecting small lesions than Octreoscan™, is now probably the preferred agent because high uptake in known sites of disease provides a diagnostic pair for assessing suitability of patients for [177Lu]DOTA-octreotate (LuTate) peptide receptor radionuclide therapy (PRRT). A range of other radiolabelled SSA has also been used for PRRT. Lesions without SSTR expression require alternative imaging and therapeutic strategies. Although fluorodeoxyglucose (FDG) uptake in low-grade NET is not generally increased relative to normal tissues, the loss of differentiation that often accompanies loss of SSTR expression may be associated with a significant increase in glycolytic metabolism and an accompanying improvement in the diagnostic sensitivity of FDG PET/CT. High FDG avidity is associated with a poorer prognosis but increases the likelihood of response to chemotherapy. Functioning tumours also require substrates for their secreted products. This can be exploited for NET imaging with amine precursor uptake being imaged using [18F]3,4-dihydrophenylalanine and serotonin-secreting tumours being sensitively detected using [11C]5-hydroxytryptamine. Both these agents are suitable for imaging with PET. [123I]meta-Iodo-benzyl-guanidine (MIBG) SPECT/CT may also be useful as a staging technique, particularly for NET of the sympathetic neuronal chain, and can identify patients who may be suitable for [131I]MIBG therapy. In the future, paradigms guided by clinical and biopsy features should allow personalised imaging paradigms aligned to therapeutic options. PMID:20880795

Identifying the heterogeneity of COPD by V/P SPECT: a new tool for improving the diagnosis of parenchymal defects and grading the severity of small airways disease.

PubMed

Bajc, M; Chen, Y; Wang, J; Li, X Y; Shen, W M; Wang, C Z; Huang, H; Lindqvist, A; He, X Y

2017-01-01

Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool. We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent. 94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry. Ventilation and perfusion defects were analyzed blindly according to the European guidelines. Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease. Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry. Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients. Emphysema was identified in 81 patients. Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor. The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages ( r =0.63 and -0.60, respectively, P <0.0001). V/P SPECT identified pulmonary embolism in 30 patients (32%). A pattern typical for heart failure was present in 26 patients (28%). Parenchymal changes typical for pneumonia or lung tumor were present in several cases. V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity. Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities. The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis.

Nuclear import of Nkx2-2 is mediated by multiple pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Wenbo; Xu, PengPeng; Guo, YingYing

Nkx2-2 homeoprotein is essential for the development of the central nervous system and pancreas. Although the nuclear localization signals of Nkx2-2 have been identified, the responsible transport receptor is still unknown. Here, we demonstrate that imp α1 not only interacts with Nkx2-2 but also transports it into the nucleus in vitro by acting together with imp β1. However, the nuclear import of Nkx2-2 in cells was not inhibited in response to knockdown expression of endogenous imp β1 or over-expression of Bimax2. Furthermore, imp β1 and imp 13, but not imp 4, directly interact with Nkx2-2 and are capable of transporting Nkx2-2more » in an in vitro import assay. By GST pull-down assay, we demonstrate that mutation of NLS1 or NLS2 has no effect on interaction with imp α1 or imp 13, but significantly reduced binding to imp β1. Thus, the nuclear import of Nkx2-2 is mediated not only by the classical import pathway but also directly by imp β1 or imp 13.« less

Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to bitter, sweet, and umami taste stimuli

PubMed Central

DeSimone, John A.; Phan, Tam-Hao T.; Ren, ZuoJun; Mummalaneni, Shobha

2012-01-01

The relationship between taste receptor cell (TRC) intracellular Ca2+ ([Ca2+]i) and rat chorda tympani (CT) nerve responses to bitter (quinine and denatonium), sweet (sucrose, glycine, and erythritol), and umami [monosodium glutamate (MSG) and MSG + inosine 5′-monophosphate (IMP)] taste stimuli was investigated before and after lingual application of ionomycin (Ca2+ ionophore) + Ca2+, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM; Ca2+ chelator), U73122 (phospholipase C blocker), thapsigargin (Ca2+-ATPase blocker), and diC8-PIP2 (synthetic phosphatidylinositol 4,5-bisphosphate). The phasic CT response to quinine was indifferent to changes in [Ca2+]i. However, a decrease in [Ca2+]i inhibited the tonic part of the CT response to quinine. The CT responses to sweet and umami stimuli were indifferent to changes in TRC [Ca2+]i. However, a decrease in [Ca2+]i attenuated the synergistic effects of ethanol on the CT response to sweet stimuli and of IMP on the glutamate CT response. U73122 and thapsigargin inhibited the phasic and tonic CT responses to bitter, sweet, and umami stimuli. Although diC8-PIP2 increased the CT response to bitter and sweet stimuli, it did not alter the CT response to glutamate but did inhibit the synergistic effect of IMP on the glutamate response. The results suggest that bitter, sweet, and umami taste qualities are transduced by [Ca2+]i-dependent and [Ca2+]i-independent mechanisms. Changes in TRC [Ca2+]i in the BAPTA-sensitive cytosolic compartment regulate quality-specific taste receptors and ion channels that are involved in the neural adaptation and mixture interactions. Changes in TRC [Ca2+]i in a separate subcompartment, sensitive to inositol trisphosphate and thapsigargin but inaccessible to BAPTA and ionomycin + Ca2+, are associated with neurotransmitter release. PMID:22993258

Intramyocardial pressure gradients in working and nonworking isolated cat hearts.

PubMed

Mihailescu, L S; Abel, F L

1994-03-01

This study presents an improved method for the measurement of intramyocardial pressure (IMP) using the servo-nulling mechanism. Glass micropipettes (20-24 microns OD) were used as transducers, coated to increase their mechanical resistance to breakage, and placed inside the left ventricular wall with a micropipette holder and manipulator. IMP was measured at the base of the left ventricle in working and nonworking isolated cat hearts that were perfused with Krebs-Henseleit buffer. In working hearts a transmural gradient of systolic IMP oriented from endocardium toward the epicardium was found; the endocardial values for systolic IMP were slightly higher than systolic left ventricular pressure (LVP), by 11-18%. Increases in afterload induced increases in IMP, without changing the systolic IMP-to-LVP ratio. In nonworking hearts with drained left ventricles, the systolic transmural gradient for IMP described for working hearts persisted, but at lower values, and was directly dependent on coronary perfusion pressure. Systolic IMP-to-LVP ratios were always > 1. The diastolic IMP of both working and nonworking hearts exhibited irregular transmural gradients. Our results support the view that generated systolic IMP is largely independent of LVP development.

Monte Carlo simulation of PET and SPECT imaging of {sup 90}Y

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Akihiko, E-mail: takahsr@hs.med.kyushu-u.ac.jp; Sasaki, Masayuki; Himuro, Kazuhiko

2015-04-15

Purpose: Yittrium-90 ({sup 90}Y) is traditionally thought of as a pure beta emitter, and is used in targeted radionuclide therapy, with imaging performed using bremsstrahlung single-photon emission computed tomography (SPECT). However, because {sup 90}Y also emits positrons through internal pair production with a very small branching ratio, positron emission tomography (PET) imaging is also available. Because of the insufficient image quality of {sup 90}Y bremsstrahlung SPECT, PET imaging has been suggested as an alternative. In this paper, the authors present the Monte Carlo-based simulation–reconstruction framework for {sup 90}Y to comprehensively analyze the PET and SPECT imaging techniques and to quantitativelymore » consider the disadvantages associated with them. Methods: Our PET and SPECT simulation modules were developed using Monte Carlo simulation of Electrons and Photons (MCEP), developed by Dr. S. Uehara. PET code (MCEP-PET) generates a sinogram, and reconstructs the tomography image using a time-of-flight ordered subset expectation maximization (TOF-OSEM) algorithm with attenuation compensation. To evaluate MCEP-PET, simulated results of {sup 18}F PET imaging were compared with the experimental results. The results confirmed that MCEP-PET can simulate the experimental results very well. The SPECT code (MCEP-SPECT) models the collimator and NaI detector system, and generates the projection images and projection data. To save the computational time, the authors adopt the prerecorded {sup 90}Y bremsstrahlung photon data calculated by MCEP. The projection data are also reconstructed using the OSEM algorithm. The authors simulated PET and SPECT images of a water phantom containing six hot spheres filled with different concentrations of {sup 90}Y without background activity. The amount of activity was 163 MBq, with an acquisition time of 40 min. Results: The simulated {sup 90}Y-PET image accurately simulated the experimental results. PET image is visually superior to SPECT image because of the low background noise. The simulation reveals that the detected photon number in SPECT is comparable to that of PET, but the large fraction (approximately 75%) of scattered and penetration photons contaminates SPECT image. The lower limit of {sup 90}Y detection in SPECT image was approximately 200 kBq/ml, while that in PET image was approximately 100 kBq/ml. Conclusions: By comparing the background noise level and the image concentration profile of both the techniques, PET image quality was determined to be superior to that of bremsstrahlung SPECT. The developed simulation codes will be very useful in the future investigations of PET and bremsstrahlung SPECT imaging of {sup 90}Y.« less

Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507

PubMed Central

Fleuren, Emmy D.G.; Versleijen-Jonkers, Yvonne M.H.; van de Luijtgaarden, Addy C.M.; Molkenboer-Kuenen, Janneke D.M.; Heskamp, Sandra; Roeffen, Melissa H.S.; van Laarhoven, Hanneke W.M.; Houghton, Peter J.; Oyen, Wim J.G.; Boerman, Otto C.; van der Graaf, Winette T.A.

2011-01-01

Purpose To investigate whether 111In-R1507 immuno-SPECT, a novel non-invasive, in vivo screening method to visualize membranous Insulin-like Growth Factor 1 Receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) responsein bone sarcomas. Experimental design BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5 and EW-8) which demonstrated high, modest or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with indium-111 labeled R1507 (111In-R1507). Biodistribution and immuno-SPECT/CT imaging studies were performed 1, 3 and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts. Results Biodistribution studies showed specific accumulation of 111In-R1507 in OS-1 and EW-5 xenografts (27.5±6.5%ID/g and 14.0±2.8%ID/g, 3 days p.i., respectively). Most importantly, 111In-R1507 uptake in IGF-1R-positive, but unresponsive, EW-8 xenografts (6.5±1.5%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5±0.6%ID/g, 3 days p.i.). Uptake in normal tissues was low and non-specific. Corresponding immuno-SPECT images clearly discriminated between high, modest and non-responding tumors by demonstrating a homogeneous (OS-1), heterogeneous (EW-5) or non-specific (EW-8 and OS-33)tumor uptake of 111In-R1507. Conclusions 111In-R1507 immuno-SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) responsein bone sarcoma patients. PMID:22038993

MicroSPECT imaging of triple negative breast cancer cell tumor xenografted in athymic mice with radioiodinated anti-ICAM-1 monoclonal antibody.

PubMed

You, Linyi; Wang, Xiangyu; Guo, Zhide; Zhang, Deliang; Zhang, Pu; Li, Jindian; Su, Xinhui; Pan, Weimin; Zhang, Xianzhong

2018-04-04

Intercellular adhesion molecule-1(ICAM-1) is a potential molecular target and biomarker for triple negative breast cancer (TNBC) therapy and diagnosis. In this study, aICAM-1 was radioiodinated with 125 I/ 131 I in high radiochemical yield and the probes for TNBC tumor targeting and radioimmunotherapy were evaluated in tumor-bearing mice. High and specific accumulation of 125 I-aICAM1 in TNBC MDA-MB-231 tumor was observed in SPECT imaging and the tumor grew was inhibited obviously by 131 I-aICAM1. Thus, the radioiodinated aICAM1 could serve as potential agents for TNBC theranostics. Copyright © 2018 Elsevier Ltd. All rights reserved.

"Hidden" bone metastasis from thyroid carcinoma: a clinical note.

PubMed

Sioka, C; Skarulis, M C; Tulloch-Reid, M K; Heiss, J D; Reynolds, J C

2014-01-01

The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Insight into stereochemistry of a new IMP allelic variant (IMP-55) metallo-β-lactamase identified in a clinical strain of Acinetobacter baumannii.

PubMed

Shakibaie, Mohammad Reza; Azizi, Omid; Shahcheraghi, Fereshteh

2017-07-01

Metallo-β-lactamases (MBLs) such as IMPs are broad-spectrum β-lactamases that inactivate virtually all β-lactam antibiotics including carbapenems. In this study, we investigated the hydrolytic activity, phylogenetic relationship, three dimensional (3D) structure including zinc binding motif of a new IMP variant (IMP-55) identified in a clinical strain of Acinetobacter baumannii (AB). AB strain 56 was isolated from an adult ICU of a teaching hospital in Kerman, Iran. It exhibited MIC 32μg/ml to imipenem and showed MBL activity. Hydrolytic property of the MBL enzyme was measured phenotypically. Presence of bla IMP gene encoded by class 1 integrons was detected by PCR-sequencing. Phylogenetic tree of IMP protein was constructed using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and 3D model including zinc binding motif was predicted by bioinformatics softwares. Analysis of IMP sequence led to the identification of a novel IMP-type designated as IMP-55 (GenBank: KU299753.1; UniprotKB: A0A0S2MTX2). Impact in term of hydrolytic activity compared to the closest variants suggested efficient imipenem hydrolysis by this enzyme. Evolutionary distance matrix assessment indicated that IMP-55 protein is not closely related to other A. baumannii IMPs, however, shared 98% homology with Escherichia coli IMP-30 (UniprotKB: A0A0C5PJR0) and Pseudomonas aeruginosa IMP-1 (UniprotKB: Q19KT1). It consisted of five α-helices, ten β-sheets and six loops. A monovalent zinc ion attached to core of enzyme via His95, His97, His157 and Cys176. Multiple amino acid sequence alignments and mutational trajectory with reported IMPs showed 4 amino acid substitutions at positions 12(Phe→Ile), 31(Asp→Glu), 172(Leu→Phe) and 185(Asn→Lys). We suggest that the pleiotropic effect of mutations due to frequent administration of imipenem is responsible for emergence of new IMP variant in our hospitals. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of haloalkaliphilic sulfur-oxidizing microorganisms with potential application in the effluent treatment of the petroleum industry.

PubMed

Olguín-Lora, P; Le Borgne, S; Castorena-Cortés, G; Roldán-Carrillo, T; Zapata-Peñasco, I; Reyes-Avila, J; Alcántara-Pérez, S

2011-02-01

Haloalkaliphilic sulfur-oxidizing mixed cultures for the treatment of alkaline-saline effluents containing sulfide were characterized and evaluated. The mixed cultures (IMP-PB, IMP-XO and IMP-TL) were obtained from Mexican alkaline soils collected in Puebla (PB), Xochimilco (XO) and Tlahuac (TL), respectively. The Ribosomal Intergenic Spacer Analysis (RISA) revealed bacteria related to Thioalkalibacterium and Thioalkalivibrio in IMP-XO and IMP-PB mixed cultures. Halomonas strains were detected in IMP-XO and IMP-TL. In addition, an uncultured Bacteroides bacterium was present in IMP-TL. Mixed cultures were evaluated at different pH and NaCl concentrations at 30°C. IMP-PB and IMP-TL expressed thiosulfate-oxidizing activity in the 7.5-10.5 pH range, whereas IMP-XO presented its maximal activity with 19.0 mg O₂ g (protein)⁻¹ min⁻¹, at pH 10.6; it was not affected by NaCl concentrations up to 1.7 M. In continuous culture, IMP-XO showed a growth rate of 15 day⁻¹, productivity of 433.4 mg(protein) l⁻¹ day⁻¹ and haloalkaliphilic sulfur-oxidizing activity was also detected up to 170 mM by means of N-methyl-diethanolamine (MDEA). Saline-alkaline soil samples are potential sources of haloalkaliphilic sulfur-oxidizing bacteria and the mixed cultures could be applied in the treatment of inorganic sulfur compounds in petroleum industry effluents under alkaline-saline conditions.

Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lever, J.R.; Hartig, P.R.; Wong, D.F.

1985-05-01

2-(/sup 125/1)-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-(/sup 123/1)-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-(/sup 125/1)-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2more » antagonist, inhibited binding. 2-(/sup 123/1)-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-((/sup 11/C)-Me)-2-Br-LSD (/sup 11/C-MBL) from (/sup 11/C)-methyl iodide and 2-Br-LSD for PET imaging trials. /sup 11/C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-(/sup 125/1)-LSD. After 30 minutes, peak tissue to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited /sup 11/C-MBL binding. /sup 11/C-MBL is a promising candidate for PET studies of S2 receptors.« less

Radiopharmaceutical therapy of patients with metastasized melanoma with the melanin-binding benzamide 131I-BA52.

PubMed

Mier, Walter; Kratochwil, Clemens; Hassel, Jessica C; Giesel, Frederik L; Beijer, Barbro; Babich, John W; Friebe, Matthias; Eisenhut, Michael; Enk, Alexander; Haberkorn, Uwe

2014-01-01

The performance of cytotoxic drugs is defined by their selectivity of uptake and action in tumor tissue. Recent clinical responses achieved by treating metastatic malignant melanoma with therapeutic modalities based on gene expression profiling showed that malignant melanoma is amenable to systemic treatment. However, these responses are not persistent, and complementary targeted treatment strategies are required for malignant melanoma. Here we provide our experience with different labeling procedures for the radioiodination of benzamides and report on initial dosimetry data and the first therapeutic application of (131)I-BA52, a novel melanin-binding benzamide in patients with metastatic malignant melanoma. Twenty-six adults with histologically documented metastasized malignant melanoma received a single dose of 235 ± 62 MBq of (123)I-BA52 for planar and SPECT/CT imaging. Nine patients were selected for radionuclide therapy and received a median of 4 GBq (minimum, 0.51 GBq; maximum, 6.60 GBq) of the β-emitting radiopharmaceutical (131)I-BA52. A trimethyltin precursor-based synthesis demonstrated high radiochemical yields in the large-scale production of radioiodinated benzamides required for clinical application. (123)I-BA52 showed specific uptake and long-term retention in tumor tissue with low transient uptake in the excretory organs. In tumor tissue, a maximum dose of 12.2 Gy per GBq of (131)I-BA52 was calculated. The highest estimated dose to a normal organ was found for the lung (mean, 3.1 Gy/GBq). No relevant acute or mid-term toxicity was observed with the doses administered until now. Even though dosimetric calculations reveal that the doses applied in this early phase of clinical application can be significantly increased, we observed antitumor effects with follow-up imaging, and single patients of the benzamide-positive cohort of patients (3/5 of the patients receiving a dose > 4.3 GBq) demonstrated a surprisingly long survival of more than 2 y. These data indicate that systemic radionuclide therapy using (131)I-BA52 as a novel approach for the therapy of malignant melanoma is of considerable potential. Future trials should be done to enhance the precision of dosimetry, validate the maximum tolerable dose, and evaluate the effectiveness of the treatment in a prospective manner.

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

PubMed

Hiramatsu, Kosuke; Yoshino, Kiyoshi; Serada, Satoshi; Yoshihara, Kosuke; Hori, Yumiko; Fujimoto, Minoru; Matsuzaki, Shinya; Egawa-Takata, Tomomi; Kobayashi, Eiji; Ueda, Yutaka; Morii, Eiichi; Enomoto, Takayuki; Naka, Tetsuji; Kimura, Tadashi

2016-03-01

Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

Struma Ovarii With Hyperthyroidism.

PubMed

Ang, Lynn P; Avram, Anca M; Lieberman, Richard W; Esfandiari, Nazanene H

2017-06-01

We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii. This case illustrates the advantage of fusion SPECT/CT imaging with planar I-WBS for diagnosis of extrathyroidal thyrotoxicosis.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

PubMed

Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

2017-04-01

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

Toward Quantitative Small Animal Pinhole SPECT: Assessment of Quantitation Accuracy Prior to Image Compensations

PubMed Central

Chen, Chia-Lin; Wang, Yuchuan; Lee, Jason J. S.; Tsui, Benjamin M. W.

2011-01-01

Purpose We assessed the quantitation accuracy of small animal pinhole single photon emission computed tomography (SPECT) under the current preclinical settings, where image compensations are not routinely applied. Procedures The effects of several common image-degrading factors and imaging parameters on quantitation accuracy were evaluated using Monte-Carlo simulation methods. Typical preclinical imaging configurations were modeled, and quantitative analyses were performed based on image reconstructions without compensating for attenuation, scatter, and limited system resolution. Results Using mouse-sized phantom studies as examples, attenuation effects alone degraded quantitation accuracy by up to −18% (Tc-99m or In-111) or −41% (I-125). The inclusion of scatter effects changed the above numbers to −12% (Tc-99m or In-111) and −21% (I-125), respectively, indicating the significance of scatter in quantitative I-125 imaging. Region-of-interest (ROI) definitions have greater impacts on regional quantitation accuracy for small sphere sources as compared to attenuation and scatter effects. For the same ROI, SPECT acquisitions using pinhole apertures of different sizes could significantly affect the outcome, whereas the use of different radii-of-rotation yielded negligible differences in quantitation accuracy for the imaging configurations simulated. Conclusions We have systematically quantified the influence of several factors affecting the quantitation accuracy of small animal pinhole SPECT. In order to consistently achieve accurate quantitation within 5% of the truth, comprehensive image compensation methods are needed. PMID:19048346

Intramuscular pressures for monitoring different tasks and muscle conditions

NASA Technical Reports Server (NTRS)

Sejersted, O. M.; Hargens, A. R.

1995-01-01

Intramuscular fluid pressure (IMP) can easily be measured in man and animals. It follows the law of Laplace which means that it is determined by the tension of the muscle fibers, the recording depth and by fiber geometry (fiber curvature or pennation angle). Thick, bulging muscles create high IMPs (up to 1000 mmHg) and force transmission to tendons becomes inefficient. High resting or postexercise IMPs are indicative of a compartment syndrome due to muscle swelling within a low-compliance osseofascial boundary. IMP increases linearly with force (torque) independent of the mode or speed of contraction (isometric, eccentric, concentric). IMP is also a much better predictor of muscle force than the EMG signal. During prolonged low-force isometric contractions, cyclic variations in IMP are seen. Since IMP influences muscle blood flow through the muscle pump, autoregulating vascular elements, and compression of the intramuscular vasculature, alterations in IMP have important implications for muscle function.

Fine-resolution voxel S values for constructing absorbed dose distributions at variable voxel size.

PubMed

Dieudonné, Arnaud; Hobbs, Robert F; Bolch, Wesley E; Sgouros, George; Gardin, Isabelle

2010-10-01

This article presents a revised voxel S values (VSVs) approach for dosimetry in targeted radiotherapy, allowing dose calculation for any voxel size and shape of a given SPECT or PET dataset. This approach represents an update to the methodology presented in MIRD pamphlet no. 17. VSVs were generated in soft tissue with a fine spatial sampling using the Monte Carlo (MC) code MCNPX for particle emissions of 9 radionuclides: (18)F, (90)Y, (99m)Tc, (111)In, (123)I, (131)I, (177)Lu, (186)Re, and (201)Tl. A specific resampling algorithm was developed to compute VSVs for desired voxel dimensions. The dose calculation was performed by convolution via a fast Hartley transform. The fine VSVs were calculated for cubic voxels of 0.5 mm for electrons and 1.0 mm for photons. Validation studies were done for (90)Y and (131)I VSV sets by comparing the revised VSV approach to direct MC simulations. The first comparison included 20 spheres with different voxel sizes (3.8-7.7 mm) and radii (4-64 voxels) and the second comparison a hepatic tumor with cubic voxels of 3.8 mm. MC simulations were done with MCNPX for both. The third comparison was performed on 2 clinical patients with the 3D-RD (3-Dimensional Radiobiologic Dosimetry) software using the EGSnrc (Electron Gamma Shower National Research Council Canada)-based MC implementation, assuming a homogeneous tissue-density distribution. For the sphere model study, the mean relative difference in the average absorbed dose was 0.20% ± 0.41% for (90)Y and -0.36% ± 0.51% for (131)I (n = 20). For the hepatic tumor, the difference in the average absorbed dose to tumor was 0.33% for (90)Y and -0.61% for (131)I and the difference in average absorbed dose to the liver was 0.25% for (90)Y and -1.35% for (131)I. The comparison with the 3D-RD software showed an average voxel-to-voxel dose ratio between 0.991 and 0.996. The calculation time was below 10 s with the VSV approach and 50 and 15 h with 3D-RD for the 2 clinical patients. This new VSV approach enables the calculation of absorbed dose based on a SPECT or PET cumulated activity map, with good agreement with direct MC methods, in a faster and more clinically compatible manner.

High prevalence of Salmonella and IMP-4-producing Enterobacteriaceae in the silver gull on Five Islands, Australia.

PubMed

Dolejska, Monika; Masarikova, Martina; Dobiasova, Hana; Jamborova, Ivana; Karpiskova, Renata; Havlicek, Martin; Carlile, Nicholas; Priddel, David; Cizek, Alois; Literak, Ivan

2016-01-01

The objective of this study was to investigate the silver gull as an indicator of environmental contamination by salmonellae and carbapenemase-producing Enterobacteriaceae (CPE) in south-east Australia. A total of 504 cloacal samples were collected from gull chicks at three nesting colonies in New South Wales, Australia [White Bay (n = 144), Five Islands (n = 200) and Montague Island (n = 160)] and were examined for salmonellae and CPE. Isolates were tested for carbapenemase genes and susceptibility to 14 antibiotics. Clonality was determined by PFGE and MLST. Genetic context and conjugative transfer of the carbapenemase gene were determined. A total of 120 CPE of 10 species, mainly Escherichia coli (n = 85), carrying the gene blaIMP-4, blaIMP-38 or blaIMP-26 were obtained from 80 (40%) gulls from Five Islands. Thirty percent of birds from this colony were colonized by salmonellae. Most isolates contained the gene within a class 1 integron showing a blaIMP-4-qacG-aacA4-catB3 array. The blaIMP gene was carried by conjugative plasmids of variable sizes (80-400 kb) and diverse replicons, including HI2-N (n = 30), HI2 (11), A/C (17), A/C-Y (2), L/M (5), I1 (1) and non-typeable (6). Despite the overall high genetic variability, common clones and plasmid types were shared by different birds and bacterial isolates, respectively. Our data demonstrate a large-scale transmission of carbapenemase-producing bacteria into wildlife, likely as a result of the feeding habits of the birds at a local waste depot. The isolates from gulls showed significant similarities with clinical isolates from Australia, suggesting the human origin of the isolates. The sources of CPE for gulls on Five Islands should be explored and proper measures applied to stop the transmission into the environment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Leg intramuscular pressures during locomotion in humans

NASA Technical Reports Server (NTRS)

Ballard, R. E.; Watenpaugh, D. E.; Breit, G. A.; Murthy, G.; Holley, D. C.; Hargens, A. R.

1998-01-01

To assess the usefulness of intramuscular pressure (IMP) measurement for studying muscle function during gait, IMP was recorded in the soleus and tibialis anterior muscles of 10 volunteers during treadmill walking and running by using transducer-tipped catheters. Soleus IMP exhibited single peaks during late-stance phase of walking [181 +/- 69 (SE) mmHg] and running (269 +/- 95 mmHg). Tibialis anterior IMP showed a biphasic response, with the largest peak (90 +/- 15 mmHg during walking and 151 +/- 25 mmHg during running) occurring shortly after heel strike. IMP magnitude increased with gait speed in both muscles. Linear regression of soleus IMP against ankle joint torque obtained by a dynamometer produced linear relationships (n = 2, r = 0.97 for both). Application of these relationships to IMP data yielded estimated peak soleus moment contributions of 0.95-1.65 N . m/kg during walking, and 1.43-2.70 N . m/kg during running. Phasic elevations of IMP during exercise are probably generated by local muscle tissue deformations due to muscle force development. Thus profiles of IMP provide a direct, reproducible index of muscle function during locomotion in humans.

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PubMed

Darr, Andreas M; Opfermann, Thomas; Niksch, Tobias; Driesch, Dominik; Marlowe, Robert J; Freesmeyer, Martin

2013-10-01

The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

SPECT myocardial perfusion imaging as an adjunct to coronary calcium score for the detection of hemodynamically significant coronary artery stenosis

PubMed Central

2012-01-01

Background Coronary artery calcifications (CAC) are markers of coronary atherosclerosis, but do not correlate well with stenosis severity. This study intended to evaluate clinical situations where a combined approach of coronary calcium scoring (CS) and nuclear stress test (SPECT-MPI) is useful for the detection of relevant CAD. Methods Patients with clinical indication for invasive coronary angiography (ICA) were included into our study during 08/2005-09/2008. At first all patients underwent CS procedure as part of the study protocol performed by either using a multidetector computed tomography (CT) scanner or a dual-source CT imager. CAC were automatically defined by dedicated software and the Agatston score was semi-automatically calculated. A stress-rest SPECT-MPI study was performed afterwards and scintigraphic images were evaluated quantitatively. Then all patients underwent ICA. Thereby significant CAD was defined as luminal stenosis ≥75% in quantitative coronary analysis (QCA) in ≥1 epicardial vessel. To compare data lacking Gaussian distribution an unpaired Wilcoxon-Test (Mann–Whitney) was used. Otherwise a Students t-test for unpaired samples was applied. Calculations were considered to be significant at a p-value of <0.05. Results We consecutively included 351 symptomatic patients (mean age: 61.2±12.3 years; range: 18–94 years; male: n=240) with a mean Agatston score of 258.5±512.2 (range: 0–4214). ICA verified exclusion of significant CAD in 66/67 (98.5%) patients without CAC. CAC was detected in remaining 284 patients. In 132/284 patients (46.5%) with CS>0 significant CAD was confirmed by ICA, and excluded in 152/284 (53.5%) patients. Sensitivity for CAD detection by CS alone was calculated as 99.2%, specificity was 30.3%, and negative predictive value was 98.5%. An additional SPECT in patients with CS>0 increased specificity to 80.9% while reducing sensitivity to 87.9%. Diagnostic accuracy was 84.2%. Conclusions In patients without CS=0 significant CAD can be excluded with a high negative predictive value by CS alone. An additional SPECT-MPI in those patients with CS>0 leads to a high diagnostic accuracy for the detection of CAD while reducing the number of patients needing invasive diagnostic procedure. PMID:23206557

Performance Evaluation of a Bedside Cardiac SPECT System

NASA Astrophysics Data System (ADS)

Studenski, Matthew T.; Gilland, David R.; Parker, Jason G.; Hammond, B.; Majewski, Stan; Weisenberger, Andrew G.; Popov, Vladimir

2009-06-01

This paper reports on the initial performance evaluation of a bedside cardiac PET/SPECT system. The system was designed to move within a hospital to image critically-ill patients, for example, those in intensive care unit (ICU) or emergency room settings, who cannot easily be transported to a conventional SPECT or PET facility. The system uses two compact (25 cm times 25 cm) detectors with pixilated NaI crystals and position sensitive PMTs. The performance is evaluated for both 140 keV (Tc-99m) and 511 keV (F-18) emitters with the system operating in single photon counting (SPECT) mode. The imaging performance metrics for both 140 keV and 511 keV included intrinsic energy resolution, spatial resolution (intrinsic, system, and reconstructed SPECT), detection sensitivity, count rate capability, and uniformity. Results demonstrated an intrinsic energy resolution of 31% at 140 keV and 23% at 511 keV, a planar intrinsic spatial resolution of 5.6 mm full width half-maximum (FWHM) at 140 keV and 6.3 mm FWHM at 511 keV, and a sensitivity of 4.15 countsmiddotmuCi-1 ldr s-1 at 140 keV and 0.67 counts ldr muCi-1 ldr s-1 at 511 keV. To further the study, a SPECT acquisition using a dynamic cardiac phantom was performed, and the resulting reconstructed images are presented.

Performance Evaluation of a Bedside Cardiac SPECT System

DOE Office of Scientific and Technical Information (OSTI.GOV)

M.T. Studenski, D.R. Gilland, J.G. Parker, B. Hammond, S. Majewski, A.G. Weisenberger, V. Popov

This paper reports on the initial performance evaluation of a bedside cardiac PET/SPECT system. The system was designed to move within a hospital to image critically-ill patients, for example, those in intensive care unit (ICU) or emergency room settings, who cannot easily be transported to a conventional SPECT or PET facility. The system uses two compact (25 cm times 25 cm) detectors with pixilated NaI crystals and position sensitive PMTs. The performance is evaluated for both 140 keV (Tc-99m) and 511 keV (F-18) emitters with the system operating in single photon counting (SPECT) mode. The imaging performance metrics for bothmore » 140 keV and 511 keV included intrinsic energy resolution, spatial resolution (intrinsic, system, and reconstructed SPECT), detection sensitivity, count rate capability, and uniformity. Results demonstrated an intrinsic energy resolution of 31% at 140 keV and 23% at 511 keV, a planar intrinsic spatial resolution of 5.6 mm full width half-maximum (FWHM) at 140 keV and 6.3 mm FWHM at 511 keV, and a sensitivity of 4.15 countsmiddotmuCi-1 ldr s-1 at 140 keV and 0.67 counts ldr muCi-1 ldr s-1 at 511 keV. To further the study, a SPECT acquisition using a dynamic cardiac phantom was performed, and the resulting reconstructed images are presented.« less

Motility screen identifies Drosophila IGF-II mRNA-binding protein--zipcode-binding protein acting in oogenesis and synaptogenesis.

PubMed

Boylan, Kristin L M; Mische, Sarah; Li, Mingang; Marqués, Guillermo; Morin, Xavier; Chia, William; Hays, Thomas S

2008-02-01

The localization of specific mRNAs can establish local protein gradients that generate and control the development of cellular asymmetries. While all evidence underscores the importance of the cytoskeleton in the transport and localization of RNAs, we have limited knowledge of how these events are regulated. Using a visual screen for motile proteins in a collection of GFP protein trap lines, we identified the Drosophila IGF-II mRNA-binding protein (Imp), an ortholog of Xenopus Vg1 RNA binding protein and chicken zipcode-binding protein. In Drosophila, Imp is part of a large, RNase-sensitive complex that is enriched in two polarized cell types, the developing oocyte and the neuron. Using time-lapse confocal microscopy, we establish that both dynein and kinesin contribute to the transport of GFP-Imp particles, and that regulation of transport in egg chambers appears to differ from that in neurons. In Drosophila, loss-of-function Imp mutations are zygotic lethal, and mutants die late as pharate adults. Imp has a function in Drosophila oogenesis that is not essential, as well as functions that are essential during embryogenesis and later development. Germline clones of Imp mutations do not block maternal mRNA localization or oocyte development, but overexpression of a specific Imp isoform disrupts dorsal/ventral polarity. We report here that loss-of-function Imp mutations, as well as Imp overexpression, can alter synaptic terminal growth. Our data show that Imp is transported to the neuromuscular junction, where it may modulate the translation of mRNA targets. In oocytes, where Imp function is not essential, we implicate a specific Imp domain in the establishment of dorsoventral polarity.

IMP series report/bibliography

NASA Technical Reports Server (NTRS)

King, J. H.

1971-01-01

The main characteristics of the IMP spacecraft and experiments are considered and the scientific knowledge gained is presented in the form of abstracts of scientific papers using IMP data. Spacecraft characteristics, including temporal and spatial coverages, are presented followed by an annotated bibliography. Experiments conducted on all IMP's (including prelaunch IMP's H and J) are described. Figures are presented showing the time histories, through the end of 1970, of magnetic field, plasma, and energetic particle experiments.

Old wine in new bottles: validating the clinical utility of SPECT in predicting cognitive performance in mild traumatic brain injury.

PubMed

Romero, Kristoffer; Lobaugh, Nancy J; Black, Sandra E; Ehrlich, Lisa; Feinstein, Anthony

2015-01-30

The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Current status of nuclear cardiology practice in Latin America and the Caribbean.

PubMed

Paez, Diana; Peix, Amalia; Orellana, Pilar; Vitola, Joao; Mut, Fernando; Gutiérrez, Claudia; Plaza, Crosby; Becic, Tarik; Dondi, Maurizio; Estrada, Enrique

2017-02-01

The burden of cardiovascular diseases (CVDs) in the world is ever growing. They represent the first cause of death worldwide and in Latin America. Nuclear cardiology has a well-established role in the management of patient with CVDs and is being increasingly integrated into the healthcare systems in the region. However, there remains variability as to the infrastructure available across the countries, in terms of existing technology, radiopharmaceuticals, and human resources. The approximate number of gamma (γ) cameras in the region is 1348, with an average of 2.25 per million population; Argentina and Brazil having the largest number. Nearly 80% of the existing cameras are single-photon emission tomography (SPECT), of which 8% are hybrid SPECT-CT systems. Positron emission tomography technology is steadily increasing, and currently, there is an average of 0.25 scanners per million inhabitants, indicating that there is a potential to expand the capacities in order to cover the needs. Four countries have nuclear reactors for research purposes, which allow the production of technetium-99 m (Argentina, Chile, Mexico and Peru), while four (Argentina, Brazil, Cuba, and Mexico) assemble 99 Mo- 99m Tc generators. As for the nuclear cardiology studies, about 80% of studies performed are gated SPECT myocardial perfusion imaging; less than 10% are multi-gated acquisition (mainly for evaluation of cardiac toxicity in cancer patients), and the other 10% correspond to other types of studies, such as viability detection, and adrenergic innervation studies with 123 I-MIBG. Physical stress is preferred, when possible, based on the clinical condition of the patient. Regarding human resources, there is an average of 1.1 physicians and 1.3 technologists per γ camera, with 0.1 medical physicists and 0.1 radiopharmacists per center in the region. The future of nuclear cardiology in Latin America and the Caribbean is encouraging, with great potential and possibilities for growth. National, regional, and international cooperation including support from scientific societies and organizations such as International Atomic Energy Agency, American Society of Nuclear Cardiology, and Latin American Association of Biology and Nuclear Medicine Societies, as well as governmental commitment are key factors for the development of the specialty. A multimodality approach in cardiac imaging will contribute to a better management of patients with CVDs.

MIG1-dependent and MIG1-independent regulation of GAL gene expression in Saccharomyces cerevisiae: role of Imp2p.

PubMed

Alberti, Adriana; Lodi, Tiziana; Ferrero, Iliana; Donnini, Claudia

2003-10-15

Imp2p (Yil154c) is a transcriptional activator involved in glucose derepression of the maltose, galactose and raffinose utilization pathways and in resistance to thermal, oxidative or osmotic stress. We analysed the role of Imp2 in the regulation of GAL genes. Imp2 was shown to have a positive effect on glucose derepression of Leloir pathway genes and their activator gene GAL4. The effect of Imp2 on galactose metabolism was shown to be partially dependent on Mig1p. The Mig1-independent role depends on Nrg1p. However, disruption of both MIG1 and NRG1 only partially relieves the glucose repression of GAL genes in the Deltaimp2 mutant, indicating that Imp2 must also have other function(s). Moreover, the interaction between IMP2 and GAL6/BLH1, a recently isolated gene involved in the regulation of GAL genes that shares with Imp2 the ability to protect cells from the glycopeptide bleomycin, was also analysed. The results suggest a major role of Imp2 in a GAL6-independent pathway. Copyright 2003 John Wiley & Sons, Ltd.

Experimental Acquisitions with ^125I on a Small Animal SPECT Device*

NASA Astrophysics Data System (ADS)

Knott, Kevin; Welsh, Robert E.; Bradley, Eric L.; Saha, Margaret S.; Kross, Brian; Majewski, Stan; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Wojcik, Randolph

2001-04-01

We have performed single photon emission computed tomography (SPECT) studies on a small animal scanning system for which the detector employed position sensitive phototubes (125 mm dia. Hamamatsu R3292 and 18 x 18 mm Hamamatsu M-64) coupled to pixelated scintillators CsI(Tl) and CsI(Na) Phantom acquisitions were used to investigate the effects of angular sampling and scan time on reconstructed image quality and noise. Results from these studies will be described and extended to in vivo studies with small animals. *Supported in part by the Thomas F. and Kate Miller Jeffress Trust, the Department of Energy, The American Diabetes Association, The National Science Foundation, the Howard Hughes Foundation and the Virginia Commonwealth Health Research Board.

Structure of Importin-α from a Filamentous Fungus in Complex with a Classical Nuclear Localization Signal.

PubMed

Bernardes, Natalia E; Takeda, Agnes A S; Dreyer, Thiago R; Freitas, Fernanda Z; Bertolini, Maria Célia; Fontes, Marcos R M

2015-01-01

Neurospora crassa is a filamentous fungus that has been extensively studied as a model organism for eukaryotic biology, providing fundamental insights into cellular processes such as cell signaling, growth and differentiation. To advance in the study of this multicellular organism, an understanding of the specific mechanisms for protein transport into the cell nucleus is essential. Importin-α (Imp-α) is the receptor for cargo proteins that contain specific nuclear localization signals (NLSs) that play a key role in the classical nuclear import pathway. Structures of Imp-α from different organisms (yeast, rice, mouse, and human) have been determined, revealing that this receptor possesses a conserved structural scaffold. However, recent studies have demonstrated that the Impα mechanism of action may vary significantly for different organisms or for different isoforms from the same organism. Therefore, structural, functional, and biophysical characterization of different Impα proteins is necessary to understand the selectivity of nuclear transport. Here, we determined the first crystal structure of an Impα from a filamentous fungus which is also the highest resolution Impα structure already solved to date (1.75 Å). In addition, we performed calorimetric analysis to determine the affinity and thermodynamic parameters of the interaction between Imp-α and the classical SV40 NLS peptide. The comparison of these data with previous studies on Impα proteins led us to demonstrate that N. crassa Imp-α possess specific features that are distinct from mammalian Imp-α but exhibit important similarities to rice Imp-α, particularly at the minor NLS binding site.

Clinical experience with (18)F-fluorodeoxyglucose positron emission tomography and (123)I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients.

PubMed

Gil, Tae Young; Lee, Do Kyung; Lee, Jung Min; Yoo, Eun Sun; Ryu, Kyung-Ha

2014-06-01

To evaluate the potential utility of (123)I-metaiodobenzylguanine ((123)I-MIBG) scintigraphy and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether (18)F-FDG PET is as beneficial as (123)I-MIBG imaging. We selected 8 NBL patients with significant residual mass after operation and who had paired (123)I-MIBG and (18)F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans. Both scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, (123)I-MIBG might be superior to (18)F-FDG PET. The sensitivity of (123)I-MIBG and (18)F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. (18)F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive (123)I-MIBG. For bone-BM metastatic sites, the sensitivity of (123)I-MIBG and (18)F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. (123)I-MIBG scan showed higher false positivity (20.8%) than (18)F-FDG PET (0%). (123)I-MIBG is superior for delineating primary tumor sites, and (18)F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.

Non-invasive preoperative assessment of basal cell carcinoma of nodular and superficial types.

PubMed

Kuzmina, Natalia; Talme, Toomas; Lapins, Jan; Emtestam, Lennart

2005-08-01

Although various biophysical properties can be used to distinguish basal cell carcinoma (BCC) tissue from normal skin, none permits typing of the tumour. In this study, we assessed nodular (NBCC) and superficial (SBCC) types of BCC using three different non-invasive instruments and placed special emphasis on their clinical value as diagnostic tools. We included 35 patients with 35 tumours (15 NBCC and 20 SBCC), which had been diagnosed clinically. All lesions were evaluated preoperatively with an instrument measuring electrical impedance (IMP). Methods for determining transepidermal water loss (TEWL) and laser Doppler (LD) were also used. Measurements were also made in healthy skin on the contralateral side as reference. The diagnosis was confirmed by histological examination. We found clear differences between the lesions and their reference values, using all three bioengineering techniques for NBCC and SBCC. The biophysical parameters of all types vary with anatomical location. Since most of the NBCC were located on the face and most SBCC on the trunk, their baseline impedance characteristics (i.e., impedance indices magnitude index (MIX) and imaginary part index (IMIX)) differed significantly. We therefore compared delta (a difference between the reference and tumour) MIX and IMIX of NBCC and SBCC instead of the absolute figures. We found no significant differences in TEWL, blood flow and IMP between the two types of BCC and attribute this to biological variation and electromagnetic noise. As with LD and TEWL, definite differences in IMP were detected between healthy skin and BCC lesions. However, at this stage of development of the bioimpedance technique, we were unable to distinguish between the two types of BCC. An improved IMP device with semi- invasive probes or a more sophisticated type of data analysis may increase the diagnostic usefulness of the IMP method.

The morphological diversity of dermatoglyphic patterns on fingers: a simple and objective method for measurement.

PubMed

Buchwald, Wiesław

2015-02-01

The paper contains a proposal for a simple way of measuring the morphological diversity of patterns on fingers. The mono/polymorphism index (Imp) is the sum of 45 mutual absolute differences between the numerical values of the patterns depending on their degree of morphological complexity. Wendt's 7-degree scale was used to quantify the patterns. The value Imp=0 denotes monomorphism, i.e., the presence of the same type of pattern on all the fingers of both hands, while high values denote a mosaic of patterns of diverse morphology (polymorphism). Elements of the individual values of the Imp index comprise mutual homolateral differences (10 differences for the fingers of the left hand and 10 differences for the right), on the basis of which an assessment was made between the sides of the body, and additionally 25 heterolateral differences. Generally, greater degree of morphological diversity in patterns is found in males, and on the fingers of the right hand in both sexes. The arithmetic mean of the Imp index differs significantly between males (55.17) and females (52.08). Its values are not directly related to the degree of morphological complexity of patterns included in the Wendt's index. There were found, however, intra-familial connections for this trait. In light of the values of the indices of correlation and association, it may be concluded that there are relatively weak but statistically significant parents-offspring relations, as well as between siblings. An objective way to determine the values of the Imp index would make it possible to use it both for the morphological characterization of dermatoglyphs in different populations and also in clinical, auxological and genetic research. Copyright © 2014 Elsevier GmbH. All rights reserved.

Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

PubMed

Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

2003-08-01

This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (P<0.01). The washout rate of 123I-BMIPP from the myocardium was faster in CHF patients than in controls (P<0.01). As the severity of the New York Heart Association (NYHA) functional class increased, the H/M ratio decreased and the washout rate increased. The washout rate of 123I-BMIPP was inversely correlated with left ventricular fractional shortening (R=-0.62, P<0.01). ACE inhibition with enalapril increased the H/M ratio on delayed images (P<0.05) and reduced the washout rate of 123I-BMIPP (P<0.05) in CHF patients. These data suggest that: (1) angiotensin II-mediated intracellular signalling activation may be a possible mechanism for the decreased myocardial uptake and enhanced washout of 123I-BMIPP in heart failure patients; and (2) the improvement in fatty acid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress †

PubMed Central

Stypinski, Daria; McQuarrie, Stephen A.; McEwan, Alexander J. B.; Wiebe, Leonard I.

2018-01-01

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220–age]. Approximately one minute before reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers rest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2β of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2β, CLTB and Vss values were comparable to those reported previously for rested volunteers. The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis. PMID:29470434

[Expression of IMP3 in osteosarcoma and its clinical significance].

PubMed

Li, Kang-hua; Huang, Yue-ping; Zhang, Jun; Li, Guo-jun; Li, Si-hong

2009-05-01

To analyze the expressional variability of IMP3 between osteosarcoma and osteochondroma and explore its clinical significance. Paraffin sections from 68 patients with osteosarcoma and 20 patients with osteochondroma were examined for the expression of IMP3 by SP immunohistochemistry. The negative, weak positive, moderate positive and strong positive expression rates of IMP3 in 68 patients with osteosarcoma were 4.41% (3/68), 22.06% (15/68), 22.74% (19/68), 45.59% (31/68), respectively, which were significantly higher than those in 20 cases of osteochondroma tissues (P<0.01). The positive expression of IMP3 in osteosarcoma was negative correlation with the 3-year survival rate of osteosarcoma patients after the operation (P<0.01). The results suggest that IMP3 plays important roles in the tumorigenesis, progress and prognosis of osteosarcoma, and the expression of IMP3 may be an important feature of osteosarcoma.

Evaluating skeletal muscle electromechanical delay with intramuscular pressure.

PubMed

Go, Shanette A; Litchy, William J; Evertz, Loribeth Q; Kaufman, Kenton R

2018-06-08

Intramuscular pressure (IMP) is the fluid pressure generated within skeletal muscle and directly reflects individual muscle tension. The purpose of this study was to assess the development of force, IMP, and electromyography (EMG) in the tibialis anterior (TA) muscle during ramped isometric contractions and evaluate electromechanical delay (EMD). Force, EMG, and IMP were simultaneously measured during ramped isometric contractions in eight young, healthy human subjects. The EMD between the onset of force and EMG activity (Δt-EMG force) and the onset of IMP and EMG activity (Δt EMG-IMP) were calculated. A statistically significant difference (p < 0.05) was found between the mean force-EMG EMD (36 ± 31 ms) and the mean IMP-EMG EMD (3 ± 21 ms). IMP reflects changes in muscle tension due to the contractile muscle elements. Copyright © 2018 Elsevier Ltd. All rights reserved.

Experiences of intervertebral motion palpation in osteopathic practice - A qualitative interview study among Swedish osteopaths.

PubMed

Sposato, Niklas S; Bjerså, Kristofer

2017-01-01

Assessment in manual therapy includes quantitative and qualitative procedures, and intervertebral motion palpation (IMP) is one of the core assessment methods in osteopathic practice. The aim of this study was to explore osteopathic practitioners' experiences of clinical decision-making and IMP as a diagnostic tool for planning and evaluation of osteopathic interventions. The study was conducted with semi-structured interviews that included eight informants. Content analysis was used as the analytical procedure. In total, three categories emerged from the analysis: strategic decision-making, diagnostic usability of IMP, and treatment applicability of IMP. The study indicated that IMP was considered relevant and was given particular importance in cases where IMP findings confirmed clinical information attained from other stages in the diagnostic process as a whole. However, IMP findings were experienced as less important if they were not correlated to other findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

IMP2, a nuclear gene controlling the mitochondrial dependence of galactose, maltose and raffinose utilization in Saccharomyces cerevisiae.

PubMed

Donnini, C; Lodi, T; Ferrero, I; Puglisi, P P

1992-02-01

The IMP2 gene of Saccharomyces cerevisiae is involved in the nucleo-mitochondrial control of maltose, galactose and raffinose utilization as shown by the inability of imp2 mutants to grow on these carbon sources in respiratory-deficient conditions or in the presence of ethidium bromide and erythromycin. The negative phenotype cannot be scored in the presence of inhibitors of respiration and oxidative phosphorylation, indicating that the role of the mitochondria in the utilization of the above-mentioned carbon sources in imp2 mutants is not at the energetical level. Mutations in the IMP2 gene also confer many phenotypic alterations in respiratory-sufficient conditions, e.g. leaky phenotype on oxidizable carbon sources, sensitivity to heat shock and sporulation deficiency. The IMP2 gene has been cloned, sequenced and disrupted. The phenotype of null imp2 mutants is indistinguishable from that of the originally isolated mutant.

Intramuscular Pressure Measurement During Locomotion in Humans

NASA Technical Reports Server (NTRS)

Ballard, Ricard E.

1996-01-01

To assess the usefulness of intramuscular pressure (IMP) measurement for studying muscle function during gait, IMP was recorded in the soleus and tibialis anterior muscles of ten volunteers during, treadmill walking, and running using transducer-tipped catheters. Soleus IMP exhibited single peaks during late-stance phase of walking (181 +/- 69 mmHg, mean +/- S.E.) and running (269 +/- 95 mmHg). Tibialis anterior IMP showed a biphasic response, with the largest peak (90 +/- 15 mmHg during walking and 151 +/- 25 mmHg during running) occurring shortly after heel strike. IMP magnitude increased with gait speed in both muscles. Linear regression of soleus IMP against ankle joint torque obtained by a dynamometer in two subjects produced linear relationships (r = 0.97). Application of these relationships to IMP data yielded estimated peak soleus moment contributions of 0.95-165 Nm/Kg during walking, and 1.43-2.70 Nm/Kg during running. IMP results from local muscle tissue deformations caused by muscle force development and thus, provides a direct, practical index of muscle function during locomotion in humans.

Combined Quarterly Technical Report Number 31. Pluribus Satellite IMP (Interface Message Provision) Development Mobile Access Terminal Network

DTIC Science & Technology

1983-12-01

Bzo I-BIO-INODE I<---->INODE 1-SIO-I BIO I 2 Hbps <-I I LINKI #1 1 B’?LY 1 #2 I LINKI 1-> 2 bps - ----- SWITCH .---- • OR N,2 11bps ->IIJPLIN I...IPROC’Rh IPROC’RI IDOWNLINKI-> 2 14bps I BIO I-BIO-INODE I<---->INODE I-BIO-I BIO I S2 bps ->I I LINKI #1 I B’FLY 1 #2 I LINKI 1-> 2 1bps " ----- + SWITCH

The Addition of SPECT/CT Lymphoscintigraphy to Breast Cancer Radiation Planning Spares Lymph Nodes Critical for Arm Drainage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheville, Andrea L., E-mail: Cheville.andrea@mayo.edu; Brinkmann, Debra H.; Ward, Shelly B.

2013-03-15

Background: This prospective cohort study was designed to determine whether the amount of radiation delivered to the nonpathological lymph nodes (LNs) that drain the arm can be significantly reduced by integrating single-photon emission computed tomography (SPECT)/computed tomography (CT) scans into radiation treatment planning. Methods: SPECT-CT scans were acquired for the 28 patients with stage I or II breast cancer and fused with the routinely obtained radiation oncology planning CT scans. Arm-draining LNs were contoured with 0.5-cm margins automatically using a threshold of 50% maximum intensity. Two treatment plans were generated: 1 per routine clinical practice (standard; STD) and the secondmore » (modified; MOD) with treatment fields modified to minimize dose to the arm-draining LNs visible on SPECT/CT images without interfering with the dosage delivered to target tissues. Participants were treated per the MOD plans. Arm volumes were measured prior to radiation and thereafter at least three subsequent 6-month intervals. Results: Sixty-eight level I-III arm-draining LNs were identified, 57% of which were inside the STD plan fields but could be blocked in the MOD plan fields. Sixty-five percent of arm-draining LNs in the STD versus 16% in the MOD plans received a mean of ≥10 Gy, and 26% in the STD versus 4% in the MOD plans received a mean of ≥40 Gy. Mean LN radiation exposure was 23.6 Gy (standard deviation 18.2) with the STD and 7.7 Gy (standard deviation 11.3) with the MOD plans (P<.001). No participant developed lymphedema. Conclusions: The integration of SPECT/CT scans into breast cancer radiation treatment planning reduces unnecessary arm-draining LN radiation exposure and may lessen the risk of lymphedema.« less

The addition of SPECT/CT lymphoscintigraphy to breast cancer radiation planning spares lymph nodes critical for arm drainage.

PubMed

Cheville, Andrea L; Brinkmann, Debra H; Ward, Shelly B; Durski, Jolanta; Laack, Nadia N; Yan, Elizabeth; Schomberg, Paula J; Garces, Yolanda I; Suman, Vera J; Petersen, Ivy A

2013-03-15

This prospective cohort study was designed to determine whether the amount of radiation delivered to the nonpathological lymph nodes (LNs) that drain the arm can be significantly reduced by integrating single-photon emission computed tomography (SPECT)/computed tomography (CT) scans into radiation treatment planning. SPECT-CT scans were acquired for the 28 patients with stage I or II breast cancer and fused with the routinely obtained radiation oncology planning CT scans. Arm-draining LNs were contoured with 0.5-cm margins automatically using a threshold of 50% maximum intensity. Two treatment plans were generated: 1 per routine clinical practice (standard; STD) and the second (modified; MOD) with treatment fields modified to minimize dose to the arm-draining LNs visible on SPECT/CT images without interfering with the dosage delivered to target tissues. Participants were treated per the MOD plans. Arm volumes were measured prior to radiation and thereafter at least three subsequent 6-month intervals. Sixty-eight level I-III arm-draining LNs were identified, 57% of which were inside the STD plan fields but could be blocked in the MOD plan fields. Sixty-five percent of arm-draining LNs in the STD versus 16% in the MOD plans received a mean of ≥10 Gy, and 26% in the STD versus 4% in the MOD plans received a mean of ≥40 Gy. Mean LN radiation exposure was 23.6 Gy (standard deviation 18.2) with the STD and 7.7 Gy (standard deviation 11.3) with the MOD plans (P<.001). No participant developed lymphedema. The integration of SPECT/CT scans into breast cancer radiation treatment planning reduces unnecessary arm-draining LN radiation exposure and may lessen the risk of lymphedema. Copyright © 2013 Elsevier Inc. All rights reserved.

Calibration and Validation of Nonpoint Source Pollution and Erosion Comparison Tool,N- SPECT, for Tropical Conditions

NASA Astrophysics Data System (ADS)

Fares, A.; Cheng, C. L.; Dogan, A.

2006-12-01

Impaired water quality caused by agriculture, urbanization, and spread of invasive species has been identified as a major factor in the degradation of coastal ecosystems in the tropics. Watershed-scale nonpoint source pollution models facilitate in evaluating effective management practices to alleviate the negative impacts of different land-use changes. The Non-Point Source Pollution and Erosion Comparison Tool (N-SPECT) is a newly released watershed model that was not previously tested under tropical conditions. The two objectives of this study were to: i) calibrate and validate N-SPECT for the Hanalei Watershed of the Hawai`ian island of Kaua`i; ii) evaluate the performance of N-SPECT under tropical conditions using the sensitivity analysis approach. Hanalei watershed has one of the wettest points on earth, Mt. Waialeale with an average annual rainfall of 11,000 mm. This rainfall decreases to 2,000 mm at the outlet of the watershed near the coast. Number of rain days is one of the major input parameters that influences N-SPECT's simulation results. This parameter was used to account for plant canopy interception losses. The watershed was divided into sub- basins to accurately distribute the number of rain days throughout the watershed. Total runoff volume predicted by the model compared well with measured data. The model underestimated measured runoff by 1% for calibration period and 5% for validation period due to higher intensity precipitation in the validation period. Sensitivity analysis revealed that the model was most sensitive to the number of rain days, followed by canopy interception, and least sensitive to the number of sub-basins. The sediment and water quality portion of the model is currently being evaluated.

Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

PubMed

Kowalski, Thomas; Siddiqui, Ali; Loren, David; Mertz, Howard R; Mallat, Damien; Haddad, Nadim; Malhotra, Nidhi; Sadowski, Brett; Lybik, Mark J; Patel, Sandeep N; Okoh, Emuejevoke; Rosenkranz, Laura; Karasik, Michael; Golioto, Michael; Linder, Jeffrey; Catalano, Marc F; Al-Haddad, Mohammad A

2016-09-01

To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

Oncofetal Protein IMP3: A Novel Molecular Marker That Predicts Metastasis of Papillary and Chromophobe Renal Cell Carcinomas

PubMed Central

Jiang, Zhong; Lohse, Christine M.; Chu, Peigou G.; Wu, Chin-Lee; Woda, Bruce A.; Rock, Kenneth L.; Kwon, Eugene D.

2009-01-01

BACKGROUND Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40–23.96; P <.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13–3.22; P =.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00–30.14; P <.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15–3.31; P =.013) compared with patients with IMP3-negative tumors. CONCLUSIONS IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. PMID:18412154

Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. Maxima challenge infection.

PubMed

Jenkins, Mark C; Stevens, Laura; O'Brien, Celia; Parker, Carolyn; Miska, Katrzyna; Konjufca, Vjollca

2018-02-14

The purpose of this study was to determine if conjugating a recombinant Eimeria maxima protein, namely EmaxIMP1, into 20 nm polystyrene nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherichia coli as a poly-His fusion protein, purified by NiNTA chromatography, and conjugated to 20 nm polystyrene NP (NP-EmaxIMP1). NP-EMaxIMP1 or control non-recombinant (NP-NR) protein were delivered per os to newly-hatched broiler chicks with subsequent booster immunizations at 3 and 21 days of age. In battery cage studies (n = 4), chickens immunized with NP-EMaxIMP1 displayed complete protection as measured by weight gain (WG) against E. maxima challenge compared to chickens immunized with NP-NR. WG in the NP-EMaxIMP1-immunized groups was identical to WG in chickens that were not infected with E. maxima infected chickens. In floor pen studies (n = 2), chickens immunized with NP-EMaxIMP1 displayed partial protection as measured by WG against E. maxima challenge compared to chickens immunized with NP-NR. In order to understand the basis for immune stimulation, newly-hatched chicks were inoculated per os with NP-EMaxIMP1 or NP-NR protein, and the small intestine, bursa, and spleen, were examined for NP localization at 1 h and 6 h post-inoculation. Within 1 h, both NP-EMaxIMP1 and NP-NR were observed in all 3 tissues. An increase was observed in the level of NP-EmaxIMP1 and NP-NR in all tissues at 6 h post-inoculation. These data indicate that 20 nm NP-EmaxIMP1 or NP-NR reached deeper tissues within hours of oral inoculation and elicited complete to partial immunity against E. maxima challenge infection. Published by Elsevier Ltd.

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

PubMed

Farahati, J; Bier, D; Scheubeck, M; Lassmann, M; Schelper, L F; Grelle, I; Hanscheid, H; Biko, J; Graefe, K H; Reiners, C

1997-03-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Effect of specific activity on organ uptake of iodine-123-meta-iodobenzylguanidine in humans.

PubMed

Farahati, J; Lassmann, M; Scheubeck, M; Bier, D; Hanscheid, H; Schelper, L; Grelle, I; Biko, J; Werner, E; Graefe, K; Reiners, C

1997-04-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activity on organ uptake of radioiodinated MIBG. the kinetics of no-carrier-added (n.c.a.) [I-123]MIBG (greater than or equal to 7.4 TBq/mu mol) were compared with those of commercial (com.) [I-123]MIBG (similar to 74 MBq/mu mol) in 3 healthy volunteers by serial imaging and blood sampling. The organ uptake of radioiodinated MIBG did not remarkably differ between the two specific activities. Due to rapid degradation a more pronounced accumulation of radioactivity was present in plasma alter n.c.a. than after com. [I-123]MIBG resulting in a higher background and thyroid activity. In addition due to a prolonged residence time of the radioactivity, the radiation exposure to organs was in general slightly higher with n.c.a. [I-123]MIBG as compared to com. [I-123]MIBG. This finding highlights the higher in vivo deiodination of n.c.a. [I-123]MIBG than of com. [I-123]MIBG in humans. In the treatment of children suffering from neuroblastoma, therefore, degradation of n.c.a. [I-123]MIBG may decrease the concentration of radioiodinated MIBG available for binding at tumor sites and result in higher radiation exposure of non-tumor tissue.

A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

PubMed

Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

2002-12-01

A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

Factors affecting volume calculation with single photon emission tomography (SPECT) method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T.H.; Lee, K.H.; Chen, D.C.P.

1985-05-01

Several factors may influence the calculation of absolute volumes (VL) from SPECT images. The effect of these factors must be established to optimize the technique. The authors investigated the following on the VL calculations: % of background (BG) subtraction, reconstruction filters, sample activity, angular sampling and edge detection methods. Transaxial images of a liver-trunk phantom filled with Tc-99m from 1 to 3 ..mu..Ci/cc were obtained in 64x64 matrix with a Siemens Rota Camera and MDS computer. Different reconstruction filters including Hanning 20,32, 64 and Butterworth 20, 32 were used. Angular samplings were performed in 3 and 6 degree increments. ROI'smore » were drawn manually and with an automatic edge detection program around the image after BG subtraction. VL's were calculated by multiplying the number of pixels within the ROI by the slice thickness and the x- and y- calibrations of each pixel. One or 2 pixel per slice thickness was applied in the calculation. An inverse correlation was found between the calculated VL and the % of BG subtraction (r=0.99 for 1,2,3 ..mu..Ci/cc activity). Based on the authors' linear regression analysis, the correct liver VL was measured with about 53% BG subtraction. The reconstruction filters, slice thickness and angular sampling had only minor effects on the calculated phantom volumes. Detection of the ROI automatically by the computer was not as accurate as the manual method. The authors conclude that the % of BG subtraction appears to be the most important factor affecting the VL calculation. With good quality control and appropriate reconstruction factors, correct VL calculations can be achieved with SPECT.« less

40 CFR 86.1370-2007 - Not-To-Exceed test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... regeneration event where regeneration is pending (state 1). (iii) If either N0 or N12 are zero, then RF cannot... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.009 Where: P = absolute intake... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.010 Where: P = absolute intake...

40 CFR 86.1370-2007 - Not-To-Exceed test procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... regeneration event where regeneration is pending (state 1). (iii) If either N0 or N12 are zero, then RF cannot... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.009 Where: P = absolute intake... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.010 Where: P = absolute intake...

40 CFR 86.1370 - Not-To-Exceed test procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... event where regeneration is pending (state 1). (iii) If either N0 or N12 are zero, then RF cannot be... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.009 Where: P = absolute intake... absolute intake manifold pressure (IMP) for the corresponding IMP: ER06oc00.010 Where: P = absolute intake...

Uterine uptake of iodine-123 metaiodobenzylguanidine during the menstrual phase of uterine cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bomanji, J.; Britton, K.E.

Radioiodinated I-123 metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes for detection of apudomas. In this paper normal physiological uptake of I-123 MIBG by the uterus during the menstrual phase of the uterine cycle is reported. It is likely that I-123 MIBG can be used to evaluate some of the problems in this context.

Control Optimization for a Dual-Mode Single-State Nuclear Shuttle,

DTIC Science & Technology

1980-01-01

Variables at a •.2 as Functions of the Pump ! Power# ..... ............ ......... 36 ’’i I ’I [ I I OIAPTER I INTRODUCTION Since the end of the Apollo...If this is not the case, the assIumption is slightly optimistic. 4. The effective pump power and the reactor-exit stagnation tempar- ature are...independent of the reactor-exit stagnation pressure. I ("Effective puImp power" is the power required to pump the propellants, assumed to be incompressible

The design of an optimal fog water collector: A theoretical analysis

NASA Astrophysics Data System (ADS)

Regalado, Carlos M.; Ritter, Axel

2016-09-01

We investigate the collection efficiency of different fog water catchers assemblies (mainly flat and cylindrical structures equipped with several screens of staggered filaments) by means of parametric equations which take into consideration both impaction and aerodynamic effects. We introduce different models that vary in complexity and range of applicability, and may be used to analyze the effect that geometry, number of screens, spacing and inclination of the filament strands have on the fog water yield of the collector. Increasing the number of impacting screens, nR, is shown to improve the collection efficiency up to an optimum for nR = 3-5; beyond nR > 5 impermeability to the airflow makes the fog catcher less efficient. Geometry of the collector is shown to be relatively important: unless wind direction varies widely, the rectangular flat design is preferred over the cylindrical one, because of its larger drag, i.e. increased aerodynamic efficiency, ηa. In fact ηa is shown to be limiting, such that values over ηa > 50% are difficult to attain. By contrast the impaction efficiency, ηimp, of fog water droplets onto multiple nR parallel screens of filaments may reach theoretical values of ηimp > 80%. Inclination of the impacting screens over the vertical may slightly reduce ηimp, but this may be compensated by a reduction in flow resistance, i.e. increased aerodynamic efficiency.

TH-E-BRF-02: 4D-CT Ventilation Image-Based IMRT Plans Are Dosimetrically Comparable to SPECT Ventilation Image-Based Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kida, S; University of Tokyo Hospital, Bunkyo, Tokyo; Bal, M

Purpose: An emerging lung ventilation imaging method based on 4D-CT can be used in radiotherapy to selectively avoid irradiating highly-functional lung regions, which may reduce pulmonary toxicity. Efforts to validate 4DCT ventilation imaging have been focused on comparison with other imaging modalities including SPECT and xenon CT. The purpose of this study was to compare 4D-CT ventilation image-based functional IMRT plans with SPECT ventilation image-based plans as reference. Methods: 4D-CT and SPECT ventilation scans were acquired for five thoracic cancer patients in an IRB-approved prospective clinical trial. The ventilation images were created by quantitative analysis of regional volume changes (amore » surrogate for ventilation) using deformable image registration of the 4D-CT images. A pair of 4D-CT ventilation and SPECT ventilation image-based IMRT plans was created for each patient. Regional ventilation information was incorporated into lung dose-volume objectives for IMRT optimization by assigning different weights on a voxel-by-voxel basis. The objectives and constraints of the other structures in the plan were kept identical. The differences in the dose-volume metrics have been evaluated and tested by a paired t-test. SPECT ventilation was used to calculate the lung functional dose-volume metrics (i.e., mean dose, V20 and effective dose) for both 4D-CT ventilation image-based and SPECT ventilation image-based plans. Results: Overall there were no statistically significant differences in any dose-volume metrics between the 4D-CT and SPECT ventilation imagebased plans. For example, the average functional mean lung dose of the 4D-CT plans was 26.1±9.15 (Gy), which was comparable to 25.2±8.60 (Gy) of the SPECT plans (p = 0.89). For other critical organs and PTV, nonsignificant differences were found as well. Conclusion: This study has demonstrated that 4D-CT ventilation image-based functional IMRT plans are dosimetrically comparable to SPECT ventilation image-based plans, providing evidence to use 4D-CT ventilation imaging for clinical applications. Supported in part by Free to Breathe Young Investigator Research Grant and NIH/NCI R01 CA 093626. The authors thank Philips Radiation Oncology Systems for the Pinnacle3 treatment planning systems.« less

Multimodal molecular imaging reveals high target uptake and specificity of 111In and 68Ga labeled fibrin-binding probes for thrombus detection in rats

PubMed Central

Oliveira, Bruno L.; Blasi, Francesco; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Caravan, Peter

2016-01-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods Radiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA) or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging. Results All three radiotracers showed similar affinity to soluble fibrin fragment DD(E) (Ki = 0.53–0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0 ± 0.2% ID/g) with low off-target accumulation. Both radiotracers underwent fast systemic elimination (t1/2 = 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation and/or degradation. Triple isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. Conclusion 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity, and represent useful PET and SPECT probes for thrombus detection. PMID:26251420

Effects of RNAi-Mediated Knockdown of Histone Methyltransferases on the Sex-Specific mRNA Expression of Imp in the Silkworm Bombyx mori

PubMed Central

Suzuki, Masataka G.; Ito, Haruka; Aoki, Fugaku

2014-01-01

Sexual differentiation in Bombyx mori is controlled by sex-specific splicing of Bmdsx, which results in the omission of exons 3 and 4 in a male-specific manner. In B. mori, insulin-like growth factor II mRNA-binding protein (Imp) is a male-specific factor involved in male-specific splicing of Bmdsx. Male-specific Imp mRNA results from the male-specific inclusion of exon 8. To verify the link between histone methylation and alternative RNA processing in Imp, we examined the effects of RNAi-mediated knockdown of several histone methyltransferases on the sex-specific mRNA expression of Imp. As a result, male-specific expression of Imp mRNA was completely abolished when expression of the H3K79 methyltransferase DOT1L was repressed to <10% of that in control males. Chromatin immunoprecipitation-quantitative PCR analysis revealed a higher distribution of H3K79me2 in normal males than in normal females across Imp. RNA polymerase II (RNAP II) processivity assays indicated that RNAi knockdown of DOT1L in males caused a twofold decrease in RNAP II processivity compared to that in control males, with almost equivalent levels to those observed in normal females. Inhibition of RNAP II-mediated elongation in male cells repressed the male-specific splicing of Imp. Our data suggest the possibility that H3K79me2 accumulation along Imp is associated with the male-specific alternative processing of Imp mRNA that results from increased RNAP II processivity. PMID:24758924

Immunophenotyping of the cerebrospinal fluid as a prognostic factor at diagnosis of acute lymphoblastic leukemia in children and adolescents.

PubMed

Cancela, Camila Silva Peres; Murao, Mitiko; Assumpção, Juliana Godoy; Souza, Marcelo Eduardo de Lima; de Macedo, Antonio Vaz; Viana, Marcos Borato; De Oliveira, Benigna Maria

2017-03-01

This study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p < 0.0001) and event-free survival (p < 0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.

Identification of expressed resistance gene analogs (RGA.) from peanut expressed sequence tage (EST.) and development of RGA-SSR markers

USDA-ARS?s Scientific Manuscript database

Cultivated peanut (Arachis hypogaea L.) is an important food and oil crop grown in more than 100 countries for providing edible oil and protein. A wide variety of pathogens including fungi, bacteria, viruses, and nematodes severely constrain peanut yield and quality. Therefore, it is very imp...

Spatial Planning: A Configuration Space Approach.

DTIC Science & Technology

1980-12-01

121. Atn impIke Cn (n.ItIion oft (is operation is NIhowin in Apple ndli 1. Sia l~m I ? I(- (A),) canl hc c(Imiptited in inear tim!1, b first...Iilc\\ arc eiiciiiiilvrA dmiong the cfiunte~ldpicwlse scall of Ihcorcm 6 slingle valuled os cithe illter-\\,a) then tile l;ipping frhi (x, !/ cos 0) to

[18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model.

PubMed

Diocou, S; Volpe, A; Jauregui-Osoro, M; Boudjemeline, M; Chuamsaamarkkee, K; Man, F; Blower, P J; Ng, T; Mullen, G E D; Fruhwirth, G O

2017-04-19

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [ 18 F]tetrafluoroborate ([ 18 F]BF 4 - ) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [ 18 F]BF 4 - (PET/CT) was compared to the conventional tracer [ 123 I]iodide (sequential SPECT/CT). We found that [ 18 F]BF 4 - was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [ 18 F]BF 4 - -PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [ 18 F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [ 18 F]BF 4 - -PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

PubMed

Macdonald, Ian R; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2016-02-01

Acetylcholinesterase and butyrylcholinesterase accumulate with brain β-amyloid (Aβ) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aβ plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aβ plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aβ accumulation, during life. Current Aβ imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aβ imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aβ and cholinesterase activity to visualize Aβ plaque load for comparison with radioligand uptake. Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aβ plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aβ plaques from both AD and cognitively normal individuals. Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aβ plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aβ plaques. Imaging cholinesterase activity associated with Aβ plaques in the living brain may contribute to the definitive diagnosis of AD during life. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Differential expression of IMP3 between male and female mature teratomas--immunohistochemical evidence of malignant nature.

PubMed

Goodman, Steven; Zhang, Liping; Cheng, Liang; Jiang, Zhong

2014-10-01

Ovarian mature teratoma is a benign tumour, whereas mature teratoma in adult testicular germ cell tumours (TGCTs) is considered to be a malignant tumour. IMP3, an oncofetal protein, plays an important role in embryogenesis and carcinogenesis. IMP3 has been demonstrated to be a malignant biomarker that is mainly expressed in malignant neoplasms rather than benign tissues. The aim of this study was to analyse IMP3 expression in germ cell tumours, and compare its expression between male and female teratomas. One hundred and seventy-eight cases (62 TGCTs, 52 ovarian teratomas, 27 metastatic testicular teratomas, and 37 cases of normal testicular tissue) obtained from the archives of two large academic medical centres were examined for IMP3 expression. Of the 62 TGCTs, 30 had mature teratoma components. IMP3 expression was present in 100% (30/30) of testicular mature teratoma components, and in 96% (26/27) of metastatic testicular teratomas. Other TGCT components also expressed IMP3 in 99% of cases (78/79). IMP3 expression was negative in all female mature teratomas. We describe for the first time an immunostaining marker that has differential expression in male and female mature teratomas, indicating that their pathogenesis differs. High expression of IMP3 in adult mature testicular teratomas supports their malignant nature. © 2014 John Wiley & Sons Ltd.

Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner

PubMed Central

Lowe, Alan R; Tang, Jeffrey H; Yassif, Jaime; Graf, Michael; Huang, William YC; Groves, Jay T; Weis, Karsten; Liphardt, Jan T

2015-01-01

Soluble karyopherins of the importin-β (impβ) family use RanGTP to transport cargos directionally through the nuclear pore complex (NPC). Whether impβ or RanGTP regulate the permeability of the NPC itself has been unknown. In this study, we identify a stable pool of impβ at the NPC. A subpopulation of this pool is rapidly turned-over by RanGTP, likely at Nup153. Impβ, but not transportin-1 (TRN1), alters the pore's permeability in a Ran-dependent manner, suggesting that impβ is a functional component of the NPC. Upon reduction of Nup153 levels, inert cargos more readily equilibrate across the NPC yet active transport is impaired. When purified impβ or TRN1 are mixed with Nup153 in vitro, higher-order, multivalent complexes form. RanGTP dissolves the impβ•Nup153 complexes but not those of TRN1•Nup153. We propose that impβ and Nup153 interact at the NPC's nuclear face to form a Ran-regulated mesh that modulates NPC permeability. DOI: http://dx.doi.org/10.7554/eLife.04052.001 PMID:25748139

Piwi Nuclear Localization and Its Regulatory Mechanism in Drosophila Ovarian Somatic Cells.

PubMed

Yashiro, Ryu; Murota, Yukiko; Nishida, Kazumichi M; Yamashiro, Haruna; Fujii, Kaede; Ogai, Asuka; Yamanaka, Soichiro; Negishi, Lumi; Siomi, Haruhiko; Siomi, Mikiko C

2018-06-19

In Drosophila ovarian somatic cells (OSCs), Piwi represses transposons transcriptionally to maintain genome integrity. Piwi nuclear localization requires the N terminus and PIWI-interacting RNA (piRNA) loading of Piwi. However, the underlying mechanism remains unknown. Here, we show that Importinα (Impα) plays a pivotal role in Piwi nuclear localization and that Piwi has a bipartite nuclear localization signal (NLS). Impα2 and Impα3 are highly expressed in OSCs, whereas Impα1 is the least expressed. Loss of Impα2 or Impα3 forces Piwi to be cytoplasmic, which is rectified by overexpression of any Impα members. Extension of Piwi-NLS with an additional Piwi-NLS leads Piwi to be imported to the nucleus in a piRNA-independent manner, whereas replacement of Piwi-NLS with SV40-NLS fails. Limited proteolysis analysis suggests that piRNA loading onto Piwi triggers conformational change, exposing the N terminus to the environment. These results suggest that Piwi autoregulates its nuclear localization by exposing the NLS to Impα upon piRNA loading. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

National Program for Inspection of Non-Federal Dams, Harrisville Pond Dam (NH 00065), Merrimack River Basin, Harrisville, New Hampshire. Phase I Inspection Report.

DTIC Science & Technology

1979-05-01

QUADRANGLE 1949* GEOOGIALSUREYAMS 6569 I-SERIES V712 LOVEWELL MOUNTAIN QUADRANGLE 1957 AMS 6570 I1-SERIES V712 ix S w9 IM IM w IMP U U U U F.ARISVILLE POND...4 UNIED STTES EW AMPSHGE DEPARTMENT OF INTERIOR MONADNOCK QUADRANGLE 1949 GEOLOGICAL SURVEY AMS 6569 I-SERIES V712 LOVEWELL MOUNTAIN QUADRANGLE 1957

Sub-Saharan Africa Report

DTIC Science & Technology

1987-03-18

controls, burdensome red tape and parastat- als remain. The general perception in the business community is that the reforms should have been introduced...to the scarcity of the Leone is the IMP conditionalty wnich has put a severe ceiling on credit facilities that would be extended by commercial...34I was brought up in a world of* contradiction» and- since I was a boy I. realised, that my- half A£ri~ i can parentage and:, half Lebanese or

Intramuscular pressure and electromyography as indexes of force during isokinetic exercise

NASA Technical Reports Server (NTRS)

Aratow, M.; Ballard, R. E.; Grenshaw, A. G.; Styf, J.; Watenpaugh, D. E.; Kahan, N. J.; Hargens, A. R.

1993-01-01

A direct method for measuring force production of specific muscles during dynamic exercise is presently unavailable. Previous studies indicate that both intramuscular pressure (IMP) and electromyography (EMG) correlate linearly with muscle contraction force during isometric exercise. The objective of this study was to compare IMP and EMG as linear assessors of muscle contraction force during dynamic exercise. IMP and surface EMG activity were recorded during concentric and eccentric isokinetic plantarflexion and dorsiflexion of the ankle joint from the tibialis anterior (TA) and soleus (SOL) muscles of nine male volunteers. Ankle torque was measured using a dynamometer, and IMP was measured via catheterization. IMP exhibited better linear correlation than EMG with ankle joint torque during concentric contractions of the SOL and the TA, as well as during eccentric contractions. IMP provides a better index of muscle contraction force than EMG during concentric and eccentric exercise through the entire range of torque. IMP reflects intrinsic mechanical properties of individual muscles, such as length-tension relationships, which EMG is unable to assess.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 andmore » Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.« less

Ras-sensitive IMP modulation of the Raf/MEK/ERK cascade through KSR1.

PubMed

Matheny, Sharon A; White, Michael A

2006-01-01

The E3 ubiquitin ligase IMP (impedes mitogenic signal propagation) was isolated as a novel Ras effector that negatively regulates ERK1/2 activation. Current evidence suggests that IMP limits the functional assembly of Raf/MEK complexes by inactivation of the KSR1 adaptor/scaffold protein. Interaction with Ras-GTP stimulates IMP autoubiquitination to relieve limitations on KSR function. The elevated sensitivity of IMP-depleted cells to ERK1/2 pathway activation suggests IMP acts as a signal threshold regulator by imposing reversible restrictions on the assembly of functional Raf/MEK/ERK kinase modules. These observations challenge commonly held concepts of signal transmission by Ras to the MAPK pathway and provide evidence for the role of amplitude modulation in tuning cellular responses to ERK1/2 pathway engagement. Here we describe details of the methods, including RNA interference, ubiquitin ligase assays, and protein complex analysis, that can be used to display the Ras-sensitive contribution of IMP to KSR-dependent modulation of the Raf/MEK/ERK pathway.

Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction.

PubMed

Wu, C; de Jong, J R; Gratama van Andel, H A; van der Have, F; Vastenhouw, B; Laverman, P; Boerman, O C; Dierckx, R A J O; Beekman, F J

2011-09-21

Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole collimation, and compare the quantitative accuracy with uniform Chang correction based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn body contours on the images obtained with three integrated optical cameras (UA-BC). Measurements in phantoms and rats containing known activities of isotopes were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom experiments, average relative errors comparing to the gold standards measured in a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%, respectively. Differences in accuracy on average between results of NUA-CT, UA-CT and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies except for (125)I (3.6% and 5.1%, respectively). All methods tested provide reasonable attenuation correction and result in high quantitative accuracy. NUA-CT shows superior accuracy except for (125)I, where other factors may have more impact on the quantitative accuracy than the selected attenuation correction.

Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collart, F.R.; Chubb, C.B.; Mirkin, B.L.

1992-07-10

IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results aremore » consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.« less

Signaling threshold regulation by the Ras effector IMP.

PubMed

Matheny, Sharon A; White, Michael A

2009-04-24

The Ras effector and E3 ligase family member IMP (impedes mitogenic signal propagation) acts as a steady-state resistor within the Raf-MEK-ERK kinase module. IMP concentrations are directly regulated by Ras, through induction of autoubiquitination, to permit productive Raf-MEK complex assembly. Inhibition of Raf-MEK pathway activation by IMP occurs through the inactivation of KSR, a scaffold/adapter protein that couples activated Raf to its substrate MEK1. The capacity of IMP to inhibit signal propagation through Raf to MEK is, in part, a consequence of disrupting KSR1 homo-oligomerization and c-Raf-B-Raf hetero-oligomerization. These observations suggest that IMP functions as a threshold modulator, controlling sensitivity of the cascade to stimulus by directly limiting the assembly of functional KSR1-dependent Raf-MEK complexes.

Development of a Cost-Effective Modular Pixelated NaI(Tl) Detector for Clinical SPECT Applications

PubMed Central

Rozler, Mike; Liang, Haoning; Chang, Wei

2013-01-01

A new pixelated detector for high-resolution clinical SPECT applications was designed and tested. The modular detector is based on a scintillator block comprised of 2.75×2.75×10 mm3 NaI(Tl) pixels and decoded by an array of 51 mm diameter single-anode PMTs. Several configurations, utilizing two types of PMTs, were evaluated using a collimated beam source to measure positioning accuracy directly. Good pixel separation was observed, with correct pixel identification ranging from 60 to 72% averaged over the entire area of the modules, depending on the PMT type and configuration. This translates to a significant improvement in positioning accuracy compared to continuous slab detectors of the same thickness, along with effective reduction of “dead” space at the edges. The observed 10% average energy resolution compares well to continuous slab detectors. The combined performance demonstrates the suitability of pixelated detectors decoded with a relatively small number of medium-sized PMTs as a cost-effective approach for high resolution clinical SPECT applications, in particular those involving curved detector geometries. PMID:24146436

Calculation of DNA strand breaks due to direct and indirect effects of Auger electrons from incorporated 123I and 125I radionuclides using the Geant4 computer code.

PubMed

Raisali, Gholamreza; Mirzakhanian, Lalageh; Masoudi, Seyed Farhad; Semsarha, Farid

2013-01-01

In this work the number of DNA single-strand breaks (SSB) and double-strand breaks (DSB) due to direct and indirect effects of Auger electrons from incorporated (123)I and (125)I have been calculated by using the Geant4-DNA toolkit. We have performed and compared the calculations for several cases: (125)I versus (123)I, source positions and direct versus indirect breaks to study the capability of the Geant4-DNA in calculations of DNA damage yields. Two different simple geometries of a 41 base pair of B-DNA have been simulated. The location of (123)I has been considered to be in (123)IdUrd and three different locations for (125)I. The results showed that the simpler geometry is sufficient for direct break calculations while indirect damage yield is more sensitive to the helical shape of DNA. For (123)I Auger electrons, the average number of DSB due to the direct hits is almost twice the DSB due to the indirect hits. Furthermore, a comparison between the average number of SSB or DSB caused by Auger electrons of (125)I and (123)I in (125)IdUrd and (123)IdUrd shows that (125)I is 1.5 times more effective than (123)I per decay. The results are in reasonable agreement with previous experimental and theoretical results which shows the applicability of the Geant-DNA toolkit in nanodosimetry calculations which benefits from the open-source accessibility with the advantage that the DNA models used in this work enable us to save the computational time. Also, the results showed that the simpler geometry is suitable for direct break calculations, while for the indirect damage yield, the more precise model is preferred.

Adaption of a corrector module to the IMP dynamics program

NASA Technical Reports Server (NTRS)

1972-01-01

The corrector module of the RAEIOS program and the IMP dynamics computer program were combined to achieve a date-fitting capability with the more general spacecraft dynamics models of the IMP program. The IMP dynamics program presents models of spacecraft dynamics for satellites with long, flexible booms. The properties of the corrector are discussed and a description is presented of the performance criteria and search logic for parameter estimation. A description is also given of the modifications made to add the corrector to the IMP program. This includes subroutine descriptions, common definitions, definition of input, and a description of output.

Effect of two non-synonymous ecto-5'-nucleotidase variants on the genetic architecture of inosine 5'-monophosphate (IMP) and its degradation products in Japanese Black beef.

PubMed

Uemoto, Yoshinobu; Ohtake, Tsuyoshi; Sasago, Nanae; Takeda, Masayuki; Abe, Tsuyoshi; Sakuma, Hironori; Kojima, Takatoshi; Sasaki, Shinji

2017-11-13

Umami is a Japanese term for the fifth basic taste and is an important sensory property of beef palatability. Inosine 5'-monophosphate (IMP) contributes to umami taste in beef. Thus, the overall change in concentration of IMP and its degradation products can potentially affect the beef palatability. In this study, we investigated the genetic architecture of IMP and its degradation products in Japanese Black beef. First, we performed genome-wide association study (GWAS), candidate gene analysis, and functional analysis to detect the causal variants that affect IMP, inosine, and hypoxanthine. Second, we evaluated the allele frequencies in the different breeds, the contribution of genetic variance, and the effect on other economical traits using the detected variants. A total of 574 Japanese Black cattle were genotyped using the Illumina BovineSNP50 BeadChip and were then used for GWAS. The results of GWAS showed that the genome-wide significant single nucleotide polymorphisms (SNPs) on BTA9 were detected for IMP, inosine, and hypoxanthine. The ecto-5'-nucleotidase (NT5E) gene, which encodes the enzyme NT5E for the extracellular degradation of IMP to inosine, was located near the significant region on BTA9. The results of candidate gene analysis and functional analysis showed that two non-synonymous SNPs (c.1318C > T and c.1475 T > A) in NT5E affected the amount of IMP and its degradation products in beef by regulating the enzymatic activity of NT5E. The Q haplotype showed a positive effect on IMP and a negative effect on the enzymatic activity of NT5E in IMP degradation. The two SNPs were under perfect linkage disequilibrium in five different breeds, and different haplotype frequencies were seen among breeds. The two SNPs contribute to about half of the total genetic variance in IMP, and the results of genetic relationship between IMP and its degradation products showed that NT5E affected the overall concentration balance of IMP and its degradation products. In addition, the SNPs in NT5E did not have an unfavorable effect on the other economical traits. Based on all the above findings taken together, two non-synonymous SNPs in NT5E would be useful for improving IMP and its degradation products by marker-assisted selection in Japanese Black cattle.

Comparison of SSS and SRS calculated from normal databases provided by QPS and 4D-MSPECT manufacturers and from identical institutional normals.

PubMed

Knollmann, Daniela; Knebel, Ingrid; Koch, Karl-Christian; Gebhard, Michael; Krohn, Thomas; Buell, Ulrich; Schaefer, Wolfgang M

2008-02-01

There is proven evidence for the importance of myocardial perfusion-single-photon emission computed tomography (SPECT) with computerised determination of summed stress and rest scores (SSS/SRS) for the diagnosis of coronary artery disease (CAD). SSS and SRS can thereby be calculated semi-quantitatively using a 20-segment model by comparing tracer-uptake with values from normal databases (NDB). Four severity-degrees for SSS and SRS are normally used: <4, 4-8, 9-13, and > or =14. Manufacturers' NDBs (M-NDBs) often do not fit the institutional (I) settings. Therefore, this study compared SSS and SRS obtained with the algorithms Quantitative Perfusion SPECT (QPS) and 4D-MSPECT using M-NDB and I-NDB. I-NDBs were obtained using QPS and 4D-MSPECT from exercise stress data (450 MBq (99m)Tc-tetrofosmin, triple-head-camera, 30 s/view, 20 views/head) from 36 men with a low post-stress test CAD probability and visually normal SPECT findings. Patient group was 60 men showing the entire CAD-spectrum referred for routine perfusion-SPECT. Stress/rest results of automatic quantification of the 60 patients were compared to M-NDB and I-NDB. After reclassifying SSS/SRS into the four severity degrees, kappa values were calculated to objectify agreement. Mean values (vs M-NDB) were 9.4 +/- 10.3 (SSS) and 5.8 +/- 9.7 (SRS) for QPS and 8.2 +/- 8.7 (SSS) and 6.2 +/- 7.8 (SRS) for 4D-MSPECT. Thirty seven of sixty SSS classifications (kappa = 0.462) and 40/60 SRS classifications (kappa = 0.457) agreed. Compared to I-NDB, mean values were 10.2 +/- 11.6 (SSS) and 6.5 +/- 10.4 (SRS) for QPS and 9.2 +/- 9.3 (SSS) and 7.2 +/- 8.6 (SRS) for 4D-MSPECT. Forty four of sixty patients agreed in SSS and SRS (kappa = 0.621 resp. 0.58). Considerable differences between SSS/SRS obtained with QPS and 4D-MSPECT were found when using M-NDB. Even using identical patients and identical I-NDB, the algorithms still gave substantial different results.

3D SPECT/CT fusion using image data projection of bone SPECT onto 3D volume-rendered CT images: feasibility and clinical impact in the diagnosis of bone metastasis.

PubMed

Ogata, Yuji; Nakahara, Tadaki; Ode, Kenichi; Matsusaka, Yohji; Katagiri, Mari; Iwabuchi, Yu; Itoh, Kazunari; Ichimura, Akira; Jinzaki, Masahiro

2017-05-01

We developed a method of image data projection of bone SPECT into 3D volume-rendered CT images for 3D SPECT/CT fusion. The aims of our study were to evaluate its feasibility and clinical usefulness. Whole-body bone scintigraphy (WB) and SPECT/CT scans were performed in 318 cancer patients using a dedicated SPECT/CT systems. Volume data of bone SPECT and CT were fused to obtain 2D SPECT/CT images. To generate our 3D SPECT/CT images, colored voxel data of bone SPECT were projected onto the corresponding location of the volume-rendered CT data after a semi-automatic bone extraction. Then, the resultant 3D images were blended with conventional volume-rendered CT images, allowing to grasp the three-dimensional relationship between bone metabolism and anatomy. WB and SPECT (WB + SPECT), 2D SPECT/CT fusion, and 3D SPECT/CT fusion were evaluated by two independent reviewers in the diagnosis of bone metastasis. The inter-observer variability and diagnostic accuracy in these three image sets were investigated using a four-point diagnostic scale. Increased bone metabolism was found in 744 metastatic sites and 1002 benign changes. On a per-lesion basis, inter-observer agreements in the diagnosis of bone metastasis were 0.72 for WB + SPECT, 0.90 for 2D SPECT/CT, and 0.89 for 3D SPECT/CT. Receiver operating characteristic analyses for the diagnostic accuracy of bone metastasis showed that WB + SPECT, 2D SPECT/CT, and 3D SPECT/CT had an area under the curve of 0.800, 0.983, and 0.983 for reader 1, 0.865, 0.992, and 0.993 for reader 2, respectively (WB + SPECT vs. 2D or 3D SPECT/CT, p < 0.001; 2D vs. 3D SPECT/CT, n.s.). The durations of interpretation of WB + SPECT, 2D SPECT/CT, and 3D SPECT/CT images were 241 ± 75, 225 ± 73, and 182 ± 71 s for reader 1 and 207 ± 72, 190 ± 73, and 179 ± 73 s for reader 2, respectively. As a result, it took shorter time to read 3D SPECT/CT images than 2D SPECT/CT (p < 0.0001) or WB + SPECT images (p < 0.0001). 3D SPECT/CT fusion offers comparable diagnostic accuracy to 2D SPECT/CT fusion. The visual effect of 3D SPECT/CT fusion facilitates reduction of reading time compared to 2D SPECT/CT fusion.

An Eimeria vaccine candidate based on Eimeria tenella immune mapped protein 1 and the TLR-5 agonist Salmonella typhimurium FliC flagellin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Guangwen; Qin, Mei; Liu, Xianyong

Highlights: •We found a new protective protein – (IMPI) in Eimeria tenella. •EtIMP1-flagellin fusion protein is an effective immunogen against Eimeria infection. •Flagellin can be as an apicomplexan parasite vaccine adjuvant in chickens. -- Abstract: Immune mapped protein-1 (IMP1) is a new protective protein in apicomplexan parasites, and exits in Eimeria tenella. But its structure and immunogenicity in E. tenella are still unknown. In this study, IMPI in E. tenella was predicted to be a membrane protein. To evaluate immunogenicity of IMPI in E. tenella, a chimeric subunit vaccine consisting of E. tenella IMP1 (EtIMP1) and a molecular adjuvant (amore » truncated flagellin, FliC) was constructed and over-expressed in Escherichia coli and its efficacy against E. tenella infection was evaluated. Three-week-old AA broiler chickens were vaccinated with the recombinant EtIMP1-truncated FliC without adjuvant or EtIMP1 with Freund’s Complete Adjuvant. Immunization of chickens with the recombinant EtIMP1-truncated FliC fusion protein resulted in stronger cellular immune responses than immunization with only recombinant EtIMP1 with adjuvant. The clinical effect of the EtIMP1-truncated FliC without adjuvant was also greater than that of the EtIMP1 with adjuvant, which was evidenced by the differences between the two groups in body weight gain, oocyst output and caecal lesions of E. tenella-challenged chickens. The results suggested that the EtIMP1-flagellin fusion protein can be used as an effective immunogen in the development of subunit vaccines against Eimeria infection. This is the first demonstration of antigen-specific protective immunity against avian coccidiosis using a recombinant flagellin as an apicomplexan parasite vaccine adjuvant in chickens.« less

33 CFR 159.123 - Coliform test: Type I devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Coliform test: Type I devices. 159.123 Section 159.123 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.123 Coliform test...

SPECT detectors: the Anger Camera and beyond

PubMed Central

Peterson, Todd E.; Furenlid, Lars R.

2011-01-01

The development of radiation detectors capable of delivering spatial information about gamma-ray interactions was one of the key enabling technologies for nuclear medicine imaging and, eventually, single-photon emission computed tomography (SPECT). The continuous NaI(Tl) scintillator crystal coupled to an array of photomultiplier tubes, almost universally referred to as the Anger Camera after its inventor, has long been the dominant SPECT detector system. Nevertheless, many alternative materials and configurations have been investigated over the years. Technological advances as well as the emerging importance of specialized applications, such as cardiac and preclinical imaging, have spurred innovation such that alternatives to the Anger Camera are now part of commercial imaging systems. Increased computing power has made it practical to apply advanced signal processing and estimation schemes to make better use of the information contained in the detector signals. In this review we discuss the key performance properties of SPECT detectors and survey developments in both scintillator and semiconductor detectors and their readouts with an eye toward some of the practical issues at least in part responsible for the continuing prevalence of the Anger Camera in the clinic. PMID:21828904

Activating PXR by Imperatorin Attenuates Dextran Sulphate Sodium-Induced Colitis in Mice.

PubMed

Liu, Meijing; Zhang, Guohui; Zheng, Chunge; Song, Meng; Liu, Fangle; Huang, Xiaotao; Bai, Shasha; Huang, Xinan; Lin, Chaozhan; Zhu, Chenchen; Hu, Yingjie; Mi, Suiqing; Liu, Changhui

2018-06-26

The activation of human pregnane X receptor (PXR) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally-occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD. The effects of IMP on PXR-modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis of CYP3A4 mRNA and protein expression levels, and measurement of CYP3A4 activity using a cell-based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF-κB activity was evaluated by a reporter assay and NF-κB p65 nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines were assessed by ELISA. IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 (SRC-1) to the ligand-binding domain of PXR, and increased the expression and activity of CYP3A4. However, PXR knockdown substantially reduced PXR-mediated CYP3A4 expression. Furthermore, IMP-mediated PXR activation suppressed NF-κB nuclear translocation and downregulated lipopolysaccharide-induced proinflammatory gene expression. Nevertheless, PXR knockdown partially reduced the IMP-mediated inhibition of NF-κB. IMP ameliorated DSS-induced colitis by PXR/NF-κB signalling. IMP serves as a PXR agonist to attenuate DSS-induced colitis by the suppression of the NF-κB-mediated proinflammatory response in a PXR/NF-κB- dependent manner. This article is protected by copyright. All rights reserved.

Impact of Internal Metallic Ports in Temporary Tissue Expanders on Postmastectomy Radiation Dose Distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Susie A.; Ogunleye, Tomiwa; Dhabbaan, Anees

Purpose: Temporary tissue expanders (TTE) with an internal magnetic metal port (IMP) have been increasingly used for breast reconstruction in post-mastectomy patients who receive radiation therapy (XRT). We evaluated XRT plans of patients with IMP to determine its effect on XRT dose distribution. Methods and Materials: Original treatment plans with CT simulation scans of 24 consecutive patients who received XRT (ORI), planned without heterogeneity corrections, to a reconstructed breast containing an IMP were used. Two additional treatment plans were then generated: one treatment plan with the IMP assigned the electron density of the rare earth magnet, nickel plated neodymium-iron-boron (HET),more » and a second treatment plan with the IMP assigned a CT value of 1 to simulate a homogeneous breast without an IMP (BRS). All plans were prescribed 50 Gy to the reconstructed breast (CTV). Results: CTV coverage by 50 Gy was significantly lower in the HET (mean 87.7% CTV) than in either the ORI (mean 99.7% CTV, P<.001) or BRS plans (mean 95.0% CTV, P<.001). The effect of the port was more pronounced on CT slices containing the IMP with prescription dose coverage of the CTV being less in the HET than in either ORI (mean difference 33.6%, P<.01) or BRS plans (mean difference 30.1%, P<.001). HET had a less homogeneous and conformal dose distribution than BRS or ORI. Conclusion: IMPs increase dose heterogeneity and reduce dose to the breast CTV through attenuation of the beam. For optimal XRT treatment, heterogeneity corrections should be used in XRT planning for patients with TTE with IMP, as the IMP impacts dose distribution.« less

Oligomerization of uridine phosphorimidazolides on montmorillonite: a model for the prebiotic synthesis of RNA on minerals

NASA Technical Reports Server (NTRS)

Ding, P. Z.; Kawamura, K.; Ferris, J. P.

1996-01-01

The 5'-phosphorimidazolide of uridine reacts on Na(+)-montmorillonite 22A in aqueous solution to give oligomers as long as 7 mers. The maximum chain length increases to 9 mers and the overall oligomer yield increases when 9:1 ImpU, A5' ppA mixtures react under the same conditions. The oligomer yield and maximum chain length decreases with the structure of the added pyrophosphate in the order A5' ppA > A5' ppU > U5' ppU. Structure analysis of individual oligomer fractions was performed by selective enzymatic hydrolyses followed by HPLC analysis of the products. The regioselectivity for 3',5'-bond formation is 80-90% in the 9:1 ImpU, A5' ppA reaction, a percentage comparable to that observed in the 9:1 ImpA, A5' ppA reaction. Oligomerization of ImpU is inhibited by addition of dA5' ppdA, and MeppA. No oligomers containing A5' ppU were products of the 9:1 ImpU,A5' ppA reaction, a finding consistent with the simple addition of the ImpU to the A5' ppA and not the rearrangement of an ImpU-A5' ppA adduct. Concentrations of lysine or arginine which were close to that of the ImpU did not inhibit oligomer formation. Treatment of Na(+)-montmorillonite with 1 M arginine yielded arginine-montmorillonite, an amino acid-mineral adduct which did not catalyze ImpU oligomerization. Neither the 4-9 mers formed in the 9:1 ImpU, A5' ppA reaction nor the 4-9 mers formed by the base hydrolysis of poly(U) served as templates for the formation of oligo(A)s.

An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLC

PubMed Central

Katakam, Prakash; Dey, Baishakhi; Hwisa, Nagiat T; Assaleh, Fathi H; Chandu, Babu R; Singla, Rajeev K; Mitra, Analava

2014-01-01

Abstract Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50–150 μg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 μg/mL for Imp-E and 0.04 μg/mL for Imp-G and the LOQ values were obtained as 0.0082 μg/mL and 0.136 μg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances. PMID:25853072

Refilling the half-empty glass--Investigating the potential role of the Interpretation Modification Paradigm for Depression (IMP-D).

PubMed

Möbius, Martin; Tendolkar, Indira; Lohner, Valerie; Baltussen, Mirte; Becker, Eni S

2015-12-01

Cognitive biases are known to cause and maintain depression. However, little research has been done on techniques targeting interpretation tendencies found in depression, despite the promising findings of anxiety studies. This paper presents two experiments, investigating the suitability of an Interpretation Modification Paradigm for Depression (IMP-D) in healthy individuals, which has already proven its effectiveness in anxiety (Beard & Amir, 2008). Different from other paradigms, the IMP-D aims at modifying an interpretation bias on response- and on a more implicit reaction time-level, making this task less susceptible to demand effects. The Word-Sentence Association Paradigm for Depression (Hindash & Amir, 2011) was modified and administered in healthy volunteers (experiment I: N = 81; experiment II: N = 105). To enhance a positive interpretation bias, endorsing benign and rejecting negative interpretations of ambiguous scenarios was reinforced through feedback. This intervention was compared to the opposite training (both experiments) and a control training (experiment II only). Both experiments revealed a significant increase in bias towards benign interpretations on the level of overt decisions, while only in the first experiment a change was found on a reaction time level. These modifications are not reflected in group-differences in emotional vulnerability. Possible limitations regarding the reliability of inter-dependent response and reaction time measures are discussed. The IMP-D is able to modify interpretation biases, but adaptations are required to maximize its beneficial effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

GATE Simulations of Small Animal SPECT for Determination of Scatter Fraction as a Function of Object Size

NASA Astrophysics Data System (ADS)

Konik, Arda; Madsen, Mark T.; Sunderland, John J.

2012-10-01

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

Affordable CZT SPECT with dose-time minimization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hugg, James W.; Harris, Brian W.; Radley, Ian

2017-03-01

PURPOSE Pixelated CdZnTe (CZT) detector arrays are used in molecular imaging applications that can enable precision medicine, including small-animal SPECT, cardiac SPECT, molecular breast imaging (MBI), and general purpose SPECT. The interplay of gamma camera, collimator, gantry motion, and image reconstruction determines image quality and dose-time-FOV tradeoffs. Both dose and exam time can be minimized without compromising diagnostic content. METHODS Integration of pixelated CZT detectors with advanced ASICs and readout electronics improves system performance. Because historically CZT was expensive, the first clinical applications were limited to small FOV. Radiation doses were initially high and exam times long. Advances have significantly improved efficiency of CZT-based molecular imaging systems and the cost has steadily declined. We have built a general purpose SPECT system using our 40 cm x 53 cm CZT gamma camera with 2 mm pixel pitch and characterized system performance. RESULTS Compared to NaI scintillator gamma cameras: intrinsic spatial resolution improved from 3.8 mm to 2.0 mm; energy resolution improved from 9.8% to <4 % at 140 keV; maximum count rate is <1.5 times higher; non-detection camera edges are reduced 3-fold. Scattered photons are greatly reduced in the photopeak energy window; image contrast is improved; and the optimal FOV is increased to the entire camera area. CONCLUSION Continual improvements in CZT detector arrays for molecular imaging, coupled with optimal collimator and image reconstruction, result in minimized dose and exam time. With CZT cost improving, affordable whole-body CZT general purpose SPECT is expected to enable precision medicine applications.

Characteristics and management of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in a tertiary hospital.

PubMed

Pang, Feng; Jia, Xiu-Qin; Song, Zhen-Zhu; Li, Yan-Hua; Wang, Bin; Zhao, Qi-Gang; Wang, Chuan-Xin; Zhang, Yi; Wang, Le-Xin

2016-03-01

The emergence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases is rare. We report an occurrence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases in a Chinese tertiary care hospital from November 2010 to December 2012. The clinical characteristics of 30 patients were described. The genetic relationship of isolates was determined by pulsed-field gel electrophoresis (PFGE). Carbapenemases were detected by modified Hodge test (MHT) and polymerase chain reactions (PCRs). Amplicons were sequenced and blasted to determine the genotype. Most infected patients were from intensive care unit and had complex and serious underlying illnesses requiring mechanical ventilation. PFGE revealed that Klebsiella pneumoniae showed two major PFGE types. Two Klebsiella oxytoca had an indistinguishable PFGE pattern, while four Enterobacter cloacae were different strains. The sequencing studies showed Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in the 23 infected patients. The majority of patients had infections with the carbapenemase-producing Enterobacteriaceae (CPE) strain, most were successfully treated with a range of antibiotics and discharged. It is important to maintain a high index of suspicion to screen for carbapenemase-producing Enterobacteriaceae strains. Rapid identification of these strains and implementation of stringent procedures are the key to prevent major outbreaks in a hospital setting.

Characterisation of a CZT detector for dosimetry of molecular radiotherapy

NASA Astrophysics Data System (ADS)

McAreavey, L. H.; Harkness-Brennan, L. J.; Colosimo, S. J.; Judson, D. S.; Boston, A. J.; Boston, H. C.; Nolan, P. J.; Flux, G. D.; Denis-Bacelar, A. M.; Harris, B.; Radley, I.; Carroll, M.

2017-03-01

A pixelated cadmium zinc telluride (CZT) detector has been characterised for the purpose of developing a quantitative single photon emission computed tomography (SPECT) system for dosimetry of molecular radiotherapy (MRT). This is the aim of the Dosimetric Imaging with CZT (DEPICT) project, which is a collaboration between the University of Liverpool, The Royal Marsden Hospital, The Royal Liverpool and Broadgreen University Hospital, and the commercial partner Kromek. CZT is a direct band gap semiconductor with superior energy resolution and stopping power compared to scintillator detectors used in current SPECT systems. The inherent detector properties have been investigated and operational parameters such as bias voltage and peaking time have been selected to optimise the performance of the system. Good energy resolution is required to discriminate γ-rays that are scattered as they are emitted from the body and within the collimator, and high photon throughput is essential due to the high activities of isotopes administered in MRT. The system has an average measured electronic noise of 3.31 keV full width at half maximum (FWHM), determined through the use of an internal pulser. The energy response of the system was measured across the energy region of interest 59.5 keV to 364.5 keV and found to be linear. The reverse bias voltage and peaking time producing the optimum FWHM and maximum photon throughput were 600 V and 0.5 μs respectively. The average dead time of the system was measured as 4.84 μs and charge sharing was quantified to be 0.71 % at 59.5 keV . A pixel sensitivity calibration map was created and planar images of the medical imaging isotopes 99mTc and 123I were acquired by coupling the device to a prototype collimator, thereby demonstrating the suitability of the detector for the DEPICT project.

Evaluation of nuclear-reactor-produced iodine-123

NASA Technical Reports Server (NTRS)

Blue, J. W.; Sodd, V. J.

1976-01-01

Iodine-123 has such great potential for nuclear medicine that all possible production methods should be considered. In this report, an experimental study related to I-123 production at a high-intensity fast-flux reactor using the reaction Xe-124(n,2n)Xe-123 is considered. The conclusion is that I-123 could be made in small quantities and the cost would be higher than the cyclotron methods presently used.

Digital Flight Control System Validation.

DTIC Science & Technology

1982-06-01

dastia Lfe syal. an ideatIled in figure I sad table 3. -Fm. sad~~b~ vaw." Tomm abm occu I A Pas sr be eveated, the Structue built upon it r must be...to base the Kseetles faiuLte pruiletles ad Specifi sytem . falue. prob- ability forat lo MoSigt will be 10 bue IMPeLASt Is the requiminas fog mnds

Hyper-dependence of breast cancer cell types on the nuclear transporter Importin β1.

PubMed

Kuusisto, Henna V; Jans, David A

2015-08-01

We previously reported that overexpression of members of the Importin (Imp) superfamily of nuclear transporters results in increased nuclear trafficking through conventional transport pathways in tumour cells. Here we show for the first time that the extent of overexpression of Impβ1 correlates with disease state in the MCF10 human breast tumour progression system. Excitingly, we find that targeting Impβ1 activity through siRNA is >30 times more efficient in decreasing the viability of malignant ductal carcinoma cells compared to isogenic non-transformed counterparts, and is highly potent and tumour selective at subnanomolar concentrations. Tumour cell selectivity of the siRNA effects was unique to Impβ1 and not other Imps, with flow cytometric analysis showing >60% increased cell death compared to controls concomitant with reduced nuclear import efficiency as indicated by confocal microscopic analysis. This hypersensitivity of malignant cell types to Impβ1 knockdown raises the exciting possibility of anti-cancer therapies targeted at Impβ1. Copyright © 2015 Elsevier B.V. All rights reserved.

Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate.

PubMed

Dhabaan, Ghulam Nasser; AbuBakar, Sazaly; Cerqueira, Gustavo Maia; Al-Haroni, Mohammed; Pang, Sui Ping; Hassan, Hamimah

2015-12-14

Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

IMP3 Expression in Borderline Tumors of the Ovary.

PubMed

El-Balat, Ahmed; Sänger, Nicole; Karn, Thomas; Becker, Sven; Holtrich, Uwe; Muallem, Zelal; Arsenic, Ruza

2017-02-01

Borderline ovarian tumors (BOTs) have a less aggressive behavior than invasive epithelial ovarian tumors. Still some patients relapse or succumb to disease. Molecular markers that reliably predict prognosis are lacking. Insulin-like growth factor II mRNA-binding protein (IMP3) has been suggested as a prognostic marker in colorectal, hepatocellular, and ovarian clear-cell carcinomas. We analyzed the expression of IMP3 by immunohistochemistry in a cohort of 140 BOT and its association with histopathological features. We found no association of IMP3 expression with patients' age, FIGO stage, microinvasion, and presence of implants. In contrast, IMP3 expression correlated to mucinous subtype of BOTs (42.2% vs. 9.5% among other subtypes) (p<0.001). IMP3 expression was found to be associated with the presence of in situ carcinoma in MBOT, but not in other subtypes (p=0.021). Expression of IMP3 in BOT is associated with the mucinous subtype and may serve as an early indicator for the development of malignant features. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Studying Spatial Resolution of CZT Detectors Using Sub-Pixel Positioning for SPECT

NASA Astrophysics Data System (ADS)

Montémont, Guillaume; Lux, Silvère; Monnet, Olivier; Stanchina, Sylvain; Verger, Loïck

2014-10-01

CZT detectors are the basic building block of a variety of new SPECT systems. Their modularity allows adapting system architecture to specific applications such as cardiac, breast, brain or small animal imaging. In semiconductors, a high number of electron-hole pairs is produced by a single interaction. This direct conversion process allows better energy and spatial resolutions than usual scintillation detectors based on NaI(Tl). However, it remains often unclear if SPECT imaging can really benefit of that performance gain. We investigate the system performance of a detection module, which is based on 5 mm thick CZT with a segmented anode having a 2.5 mm pitch by simulation and experimentation. This pitch allows an easy assembly of the crystal on the readout board and limits the space occupied by electronics without significantly degrading energy and spatial resolution.

Self-vapor cooled targets for production of I-123 at high current accelerators. [using Xe-123 production

NASA Technical Reports Server (NTRS)

Blue, J. W.; Scholz, K. L.; Sodd, V. J.

1974-01-01

The basic elements of the vapor cooled target system are shown. This system can be operated as a heat pipe or as a conventional condenser. The choice of target fluid is based on the specific nuclear reaction chosen to produce Xe-123. The reaction using I-127 was studied and shown to have a significant yield for bombarding energies from 47 to 63 MeV. The Cs-133 reaction is also included. Xenon-123 is applied to I-123 production in a purer form for thyroid studies.

iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

PubMed

Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

2015-10-01

To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

Mature DIABLO/Smac Is Produced by the IMP Protease Complex on the Mitochondrial Inner Membrane

PubMed Central

Burri, Lena; Strahm, Yvan; Hawkins, Christine J.; Gentle, Ian E.; Puryer, Michelle A.; Verhagen, Anne; Callus, Bernard; Vaux, David; Lithgow, Trevor

2005-01-01

DIABLO/Smac is a mitochondrial protein that can promote apoptosis by promoting the release and activation of caspases. To do so, DIABLO/Smac must first be processed by a mitochondrial protease and then released into the cytosol, and we show this in an intact cellular system. We propose that the precursor form of DIABLO/Smac enters the mitochondria through a stop-transfer pathway and is processed to its active form by the inner membrane peptidase (IMP) complex. Catalytic subunits of the mammalian IMP complex were identified based on sequence conservation and functional complementation, and the novel sequence motif RX5P in Imp1 and NX5S in Imp2 distinguish the two catalytic subunits. DIABLO/Smac is one of only a few specific proteins identified as substrates for the IMP complex in the mitochondrial intermembrane space. PMID:15814844

A Computer Model for the Transmission Characteristics of Dielectric Radomes

DTIC Science & Technology

1992-03-01

GAUS.F....... 104 APPENDIX D........................105 A. ARGUMENTS: CIRCTHETA. CIRCRHO AND CIRCPHI . . . 105 B. TEST PROGRAM: CIRCSUB.F...ETSCAT(500),EPSCAT(500),ETHF(500),EPHF(500) INTEGER NT,NPHI,CNRHO,CNPHI,NP,SELECTION REAL MODE,BASE,RS,ZP, RHB ,ZHB DATA PI,START,STOP/3.1415926,0.,90...ZH(I)).LT..OO1) ZH(I)=O. IF(ABS(RH(I)).LT..O01) RH(I)=O. ZHB=ZH (I) /BK RHB =RH (I) /BK ZiG (i)=IMP C C ASSIGN SURFACE IMPEDANCE AT THIS POINT. THE

An Investigation Into the Relationship Between Maximum Isometric Strength and Vertical Jump Performance.

PubMed

Thomas, Christopher; Jones, Paul A; Rothwell, James; Chiang, Chieh Y; Comfort, Paul

2015-08-01

Research has demonstrated a clear relationship between dynamic strength and vertical jump (VJ) performance; however, the relationship of isometric strength and VJ performance has been studied less extensively. The aim of this study was to determine the relationship between isometric strength and performance during the squat jump (SJ) and countermovement jump (CMJ). Twenty-two male collegiate athletes (mean ± SD; age = 21.3 ± 2.9 years; height = 175.63 ± 8.23 cm; body mass = 78.06 ± 10.77 kg) performed isometric midthigh pulls (IMTPs) to assess isometric peak force (IPF), maximum rate of force development, and impulse (IMP) (I100, I200, and I300). Force-time data, collected during the VJs, were used to calculate peak velocity, peak force (PF), peak power (PP), and jump height. Absolute IMTP measures of IMP showed the strongest correlations with VJ PF (r = 0.43-0.64; p ≤ 0.05) and VJ PP (r = 0.38-0.60; p ≤ 0.05). No statistical difference was observed in CMJ height (0.33 ± 0.05 m vs. 0.36 ± 0.05 m; p = 0.19; ES = -0.29) and SJ height performance (0.29 ± 0.06 m vs. 0.33 ± 0.05 m; p = 0.14; ES = -0.34) when comparing stronger to weaker athletes. The results of this study illustrate that absolute IPF and IMP are related to VJ PF and PP but not VJ height. Because stronger athletes did not jump higher than weaker athletes, dynamic strength tests may be more practical methods of assessing the relationships between relative strength levels and dynamic performance in collegiate athletes.

Progress in SPECT/CT imaging of prostate cancer.

PubMed

Seo, Youngho; Franc, Benjamin L; Hawkins, Randall A; Wong, Kenneth H; Hasegawa, Bruce H

2006-08-01

Prostate cancer is the most common type of cancer (other than skin cancer) among men in the United States. Although prostate cancer is one of the few cancers that grow so slowly that it may never threaten the lives of some patients, it can be lethal once metastasized. Indium-111 capromab pendetide (ProstaScint, Cytogen Corporation, Princeton, NJ) imaging is indicated for staging and recurrence detection of the disease, and is particularly useful to determine whether or not the disease has spread to distant metastatic sites. However, the interpretation of 111In-capromab pendetide is challenging without correlated structural information mostly because the radiopharmaceutical demonstrates nonspecific uptake in the normal vasculature, bowel, bone marrow, and the prostate gland. We developed an improved method of imaging and localizing 111In-Capromab pendetide using a SPECT/CT imaging system. The specific goals included: i) development and application of a novel iterative SPECT reconstruction algorithm that utilizes a priori information from coregistered CT; and ii) assessment of clinical impact of adding SPECT/CT for prostate cancer imaging with capromab pendetide utilizing the standard and novel reconstruction techniques. Patient imaging studies with capromab pendetide were performed from 1999 to 2004 using two different SPECT/CT scanners, a prototype SPECT/CT system and a commercial SPECT/CT system (Discovery VH, GE Healthcare, Waukesha, WI). SPECT projection data from both systems were reconstructed using an experimental iterative algorithm that compensates for both photon attenuation and collimator blurring. In addition, the data obtained from the commercial system were reconstructed with attenuation correction using an OSEM reconstruction supplied by the camera manufacturer for routine clinical interpretation. For 12 sets of patient data, SPECT images reconstructed using the experimental algorithm were interpreted separately and compared with interpretation of images obtained using the standard reconstruction technique. The experimental reconstruction algorithm improved spatial resolution, reduced streak artifacts, and yielded a better correlation with anatomic details of CT in comparison to conventional reconstruction methods (e.g., filtered back-projection or OSEM with attenuation correction only). Images produced with the experimental algorithm produced a subjective improvement in the confidence of interpretation for 11 of 12 studies. There were also changes in interpretations for 4 of 12 studies although the changes were not sufficient to alter prognosis or the patient treatment plan.

Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia.

PubMed

Richter, W S; Fischer, S; Ernst, N; Munz, D L

2001-07-01

Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.

13 CFR 123.200 - Am I eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2014 CFR

2014-01-01

... physical disaster business loan? 123.200 Section 123.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.200 Am I eligible to apply for a physical disaster business loan? (a) Almost any business concern or charitable or other non-profit entity...

13 CFR 123.100 - Am I eligible to apply for a home disaster loan?

Code of Federal Regulations, 2012 CFR

2012-01-01

... disaster loan? 123.100 Section 123.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.100 Am I eligible to apply for a home disaster loan? (a) You are eligible to apply for a home disaster loan if you: (1) Own and occupy your primary residence...

13 CFR 123.100 - Am I eligible to apply for a home disaster loan?

Code of Federal Regulations, 2010 CFR

2010-01-01

... disaster loan? 123.100 Section 123.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.100 Am I eligible to apply for a home disaster loan? (a) You are eligible to apply for a home disaster loan if you: (1) Own and occupy your primary residence...

13 CFR 123.201 - When am I not eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2013 CFR

2013-01-01

... for a physical disaster business loan? 123.201 Section 123.201 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.201 When am I not eligible to apply for a physical disaster business loan? (a) You are not eligible for a physical disaster...

13 CFR 123.201 - When am I not eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2014 CFR

2014-01-01

... for a physical disaster business loan? 123.201 Section 123.201 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.201 When am I not eligible to apply for a physical disaster business loan? (a) You are not eligible for a physical disaster...

13 CFR 123.104 - What interest rate will I pay on my home disaster loan?

Code of Federal Regulations, 2014 CFR

2014-01-01

... my home disaster loan? 123.104 Section 123.104 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.104 What interest rate will I pay on my home disaster loan? If you can obtain credit elsewhere, your interest rate is set by a statutory formula, but...

13 CFR 123.200 - Am I eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2012 CFR

2012-01-01

... physical disaster business loan? 123.200 Section 123.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.200 Am I eligible to apply for a physical disaster business loan? (a) Almost any business concern or charitable or other non-profit entity...

13 CFR 123.100 - Am I eligible to apply for a home disaster loan?

Code of Federal Regulations, 2014 CFR

2014-01-01

... disaster loan? 123.100 Section 123.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.100 Am I eligible to apply for a home disaster loan? (a) You are eligible to apply for a home disaster loan if you: (1) Own and occupy your primary residence...

13 CFR 123.104 - What interest rate will I pay on my home disaster loan?

Code of Federal Regulations, 2013 CFR

2013-01-01

... my home disaster loan? 123.104 Section 123.104 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.104 What interest rate will I pay on my home disaster loan? If you can obtain credit elsewhere, your interest rate is set by a statutory formula, but...

13 CFR 123.104 - What interest rate will I pay on my home disaster loan?

Code of Federal Regulations, 2012 CFR

2012-01-01

... my home disaster loan? 123.104 Section 123.104 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.104 What interest rate will I pay on my home disaster loan? If you can obtain credit elsewhere, your interest rate is set by a statutory formula, but...

13 CFR 123.201 - When am I not eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2012 CFR

2012-01-01

... for a physical disaster business loan? 123.201 Section 123.201 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.201 When am I not eligible to apply for a physical disaster business loan? (a) You are not eligible for a physical disaster...

13 CFR 123.200 - Am I eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2013 CFR

2013-01-01

... physical disaster business loan? 123.200 Section 123.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.200 Am I eligible to apply for a physical disaster business loan? (a) Almost any business concern or charitable or other non-profit entity...

13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

Code of Federal Regulations, 2010 CFR

2010-01-01

...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... disaster loan to repair or replace your damaged primary residence and personal property. [67 FR 62337, Oct...

13 CFR 123.104 - What interest rate will I pay on my home disaster loan?

Code of Federal Regulations, 2011 CFR

2011-01-01

... my home disaster loan? 123.104 Section 123.104 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.104 What interest rate will I pay on my home disaster loan? If you can obtain credit elsewhere, your interest rate is set by a statutory formula, but...

13 CFR 123.200 - Am I eligible to apply for a physical disaster business loan?

Code of Federal Regulations, 2011 CFR

2011-01-01

... physical disaster business loan? 123.200 Section 123.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.200 Am I eligible to apply for a physical disaster business loan? (a) Almost any business concern or charitable or other non-profit entity...

13 CFR 123.100 - Am I eligible to apply for a home disaster loan?

Code of Federal Regulations, 2011 CFR

2011-01-01

... disaster loan? 123.100 Section 123.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.100 Am I eligible to apply for a home disaster loan? (a) You are eligible to apply for a home disaster loan if you: (1) Own and occupy your primary residence...

13 CFR 123.100 - Am I eligible to apply for a home disaster loan?

Code of Federal Regulations, 2013 CFR

2013-01-01

... disaster loan? 123.100 Section 123.100 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.100 Am I eligible to apply for a home disaster loan? (a) You are eligible to apply for a home disaster loan if you: (1) Own and occupy your primary residence...

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

PubMed

Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elimination of soluble sup 123 I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halma, C.; Breedveld, F.C.; Daha, M.R.

1991-04-01

Using soluble {sup 123}I-labeled aggregates of human IgG ({sup 123}I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of {sup 123}I-AHIgG to erythrocytes and a faster initial rate of elimination of {sup 123}I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen.more » However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of {sup 123}I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.« less

State-of-the-art radiological techniques improve the assessment of postoperative lung function in patients with non-small cell lung cancer.

PubMed

Ohno, Yoshiharu; Koyama, Hisanobu; Nogami, Munenobu; Takenaka, Daisuke; Onishi, Yumiko; Matsumoto, Keiko; Matsumoto, Sumiaki; Maniwa, Yoshimasa; Yoshimura, Masahiro; Nishimura, Yoshihiro; Sugimura, Kazuro

2011-01-01

The purpose of this study was to compare predictive capabilities for postoperative lung function in non-small cell lung cancer (NSCLC) patients of the state-of-the-art radiological methods including perfusion MRI, quantitative CT and SPECT/CT with that of anatomical method (i.e. qualitative CT) and traditional nuclear medicine methods such as planar imaging and SPECT. Perfusion MRI, CT, nuclear medicine study and measurements of %FEV(1) before and after lung resection were performed for 229 NSCLC patients (125 men and 104 women). For perfusion MRI, postoperative %FEV(1) (po%FEV(1)) was predicted from semi-quantitatively assessed blood volumes within total and resected lungs, for quantitative CT, it was predicted from the functional lung volumes within total and resected lungs, for qualitative CT, from the number of segments of total and resected lungs, and for nuclear medicine studies, from uptakes within total and resected lungs. All SPECTs were automatically co-registered with CTs for preparation of SPECT/CTs. Predicted po%FEV(1)s were then correlated with actual po%FEV(1)s, which were measured %FEV(1)s after operation. The limits of agreement were also evaluated. All predicted po%FEV(1)s showed good correlation with actual po%FEV(1)s (0.83≤r≤0.88, p<0.0001). Perfusion MRI, quantitative CT and SPECT/CT demonstrated better correlation than other methods. The limits of agreement of perfusion MRI (4.4±14.2%), quantitative CT (4.7±14.2%) and SPECT/CT (5.1±14.7%) were less than those of qualitative CT (6.0±17.4%), planar imaging (5.8±18.2%), and SPECT (5.5±16.8%). State-of-the-art radiological methods can predict postoperative lung function in NSCLC patients more accurately than traditional methods. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of 111In- and 68Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats.

PubMed

Oliveira, Bruno L; Blasi, Francesco; Rietz, Tyson A; Rotile, Nicholas J; Day, Helen; Caravan, Peter

2015-10-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F PET probes for noninvasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and SPECT. In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in 2 animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Radiotracers were synthesized using a known fibrin-binding peptide conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DOTA-MA), or a diethylenetriamine ligand (DETA-propanoic acid [PA]), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA), or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics, and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a nonbinding control probe using SPECT/PET/CT imaging. All 3 radiotracers showed affinity similar to soluble fibrin fragment DD(E) (inhibition constant=0.53-0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0±0.2 percentage injected dose per gram), with low off-target accumulation. Both radiotracers underwent fast systemic elimination (half-life, 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation or degradation. Triple-isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity and represent useful PET and SPECT probes for thrombus detection. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Sub-Micrometer Au@PDA-125 I Particles as Theranostic Embolism Beads for Radiosensitization and SPECT/CT Monitoring.

PubMed

Sun, Gaofeng; Wang, Tao; Li, Xiao; Li, Danni; Peng, Ye; Wang, Xiaoke; Jia, Guorong; Su, Weiwei; Cheng, Chao; Yang, Jian; Zuo, Changjing

2018-05-29

Au nanoparticles (3.8 ± 0.6 nm) are assembled to sub-micrometer Au particles (186.3 ± 20.4 nm) and covered with adhesive polydopamine (PDA) as embolism beads (198.8 ± 23.2 nm). Radioactive iodine-125 is labeled to Au@PDA to introduce the function of intra-irradiation. For the therapeutic effects of Au@PDA- 125 I, Au particles sensitize the radiation to MHCC97H hepatoma cells and tumor-bearing mice. At the cellular level, after being treated with a relatively low-dose (5 Gy) γ-ray, Au-sensitized radiotherapy (RT) leads to an immediate increase of intracellular reactive oxygen species, accompanying with an increase of cell apoptosis. Due to the intra-irradiation, self-healing of RT-leaded DNA double-strand breakage is suppressed, inducing a further increase of cell apoptosis after RT treatment. Likewise, 3 cycles of sensitized RT leads to a valid control of tumor volume growth, but Au@PDA- 125 I has no harm or radioactive residual on or in the radiosensitive organs, including the thyroid, heart, lungs, liver, and spleen. Additionally, photons emitted from 125 I and high X-ray absorption of the Au element makes the beads suitable for single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Therefore, as theranostic embolism beads, Au@PDA- 125 I can both enhance the therapeutic effects of external RT, and provide a real-time SPECT/CT monitoring of therapeutic time window. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Large bond-dimension time-evolution block decimation study of the XXZ quantum spin chains of S = 1/2 and 1

NASA Astrophysics Data System (ADS)

Choi, Hwan Bin; Lee, Ji-Woo

2017-09-01

We study quantum phase transitions of a XXZ spin model with spin S = 1/2 and 1 in one dimension. The XXZ spin chain is one of basic models in understanding various one-dimensional magnetic materials. To study this model, we construct infinite-lattice matrix product state (iMPS), which is a tensor product form for a one-dimensional many-body quantum wave function. By using timeevolution- block-decimation method (TEBD) on iMPS, we obtain the ground states of the XXZ model at zero temperature. This method is very delicate in calculating ground states so that we developed a reliable method of finding the ground state with the dimension of entanglement coefficients up to 300, which is beyond the previous works. By analyzing ground-state energies, half-chain entanglement entropies, and entanglement spectrum, we found the signatures of quantum phase transitions between ferromagnetic phase, XY phase, Haldane phase, and antiferromagnetic phase.

Targets for producing high purity I-123

NASA Technical Reports Server (NTRS)

Blue, J. W. (Inventor)

1978-01-01

Tellurium powder in improved targets is bombarded with a cyclotron beam to produce Xe-123. Flowing gas streams carry the Xe-123 through one cold trap which removes Xe-123 that subsequently decays to I-123. During this bombardment energy is deposited in the target material causing its temperature to rise. Some of the tellurium vaporizes and subsequently condenses on surfaces that are cooler than the vaporization temperature. Provision is made for the repeated bombardment of this condensed tellurium.

Effects of Different Containers on Radioactivity Measurements using a Dose Calibrator with Special Reference to 111In and 123I.

PubMed

Inoue, Yusuke; Abe, Yutaka; Kikuchi, Kei; Miyatake, Hiroki; Watanabe, Atsushi

2017-01-01

Low-energy characteristic x-rays emitted by 111 In and 123 I sources are easily absorbed by the containers of the sources, affecting radioactivity measurements using a dose calibrator. We examined the effects of different containers on the estimated activities. The radioactivities of 111 In, 123 I, 201 Tl, and 99m Tc were measured in containers frequently employed in clinical practice in Japan. The 111 In measurements were performed in the vials A and B of the 111 In-pentetreotide preparation kit and in the plastic syringe. The activities of 123 I-metaiodobenzylguanidine and 201 Tl chloride were measured in the prefilled glass syringes and plastic syringes. The milking vial, vial A, vial B, and plastic syringe were used to assay 99m Tc. For 111 In and 123 I, measurements were performed with and without a copper filter. The filter was inserted into the well of the dose calibrator to absorb low-energy x-rays. The relative estimate was defined as the ratio of the activity estimated with the dose calibrator to the standard activity. The estimated activities varied greatly depending on the container when 111 In and 123 I sources were assayed without the copper filter. The relative estimates of 111 In were 0.908, 1.072, and 1.373 in the vial A, vial B, and plastic syringe, respectively. The relative estimates of 123 I were 1.052 and 1.352 in the glass syringe and plastic syringe, respectively. Use of the copper filter eliminated the container-dependence in 111 In and 123 I measurements. Container-dependence was demonstrated in neither 201 Tl nor 99m Tc measurements. The activities of 111 In and 123 I estimated with a dose calibrator differ greatly among the containers. Accurate estimation may be attained using the container-specific correction factor or using the copper filter.

Comparison of conventional and cadmium-zinc-telluride single-photon emission computed tomography for analysis of thallium-201 myocardial perfusion imaging: an exploratory study in normal databases for different ethnicities.

PubMed

Ishihara, Masaru; Onoguchi, Masahisa; Taniguchi, Yasuyo; Shibutani, Takayuki

2017-12-01

The aim of this study was to clarify the differences in thallium-201-chloride (thallium-201) myocardial perfusion imaging (MPI) scans evaluated by conventional anger-type single-photon emission computed tomography (conventional SPECT) versus cadmium-zinc-telluride SPECT (CZT SPECT) imaging in normal databases for different ethnic groups. MPI scans from 81 consecutive Japanese patients were examined using conventional SPECT and CZT SPECT and analyzed with the pre-installed quantitative perfusion SPECT (QPS) software. We compared the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) for the two SPECT devices. For a normal MPI reference, we usually use Japanese databases for MPI created by the Japanese Society of Nuclear Medicine, which can be used with conventional SPECT but not with CZT SPECT. In this study, we used new Japanese normal databases constructed in our institution to compare conventional and CZT SPECT. Compared with conventional SPECT, CZT SPECT showed lower SSS (p < 0.001), SRS (p = 0.001), and SDS (p = 0.189) using the pre-installed SPECT database. In contrast, CZT SPECT showed no significant difference from conventional SPECT in QPS analysis using the normal databases from our institution. Myocardial perfusion analyses by CZT SPECT should be evaluated using normal databases based on the ethnic group being evaluated.

Local requirement of the Drosophila insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions.

PubMed

Sarraf-Zadeh, Ladan; Christen, Stefan; Sauer, Uwe; Cognigni, Paola; Miguel-Aliaga, Irene; Stocker, Hugo; Köhler, Katja; Hafen, Ernst

2013-09-01

In Drosophila, growth takes place during the larval stages until the formation of the pupa. Starvation delays pupariation to allow prolonged feeding, ensuring that the animal reaches an appropriate size to form a fertile adult. Pupariation is induced by a peak of the steroid hormone ecdysone produced by the prothoracic gland (PG) after larvae have reached a certain body mass. Local downregulation of the insulin/insulin-like growth factor signaling (IIS) activity in the PG interferes with ecdysone production, indicating that IIS activity in the PG couples the nutritional state to development. However, the underlying mechanism is not well understood. In this study we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2), a growth inhibitor in Drosophila, is involved in this process. Imp-L2 inhibits the activity of the Drosophila insulin-like peptides by direct binding and is expressed by specific cells in the brain, the ring gland, the gut and the fat body. We demonstrate that Imp-L2 is required to regulate and adapt developmental timing to nutritional conditions by regulating IIS activity in the PG. Increasing Imp-L2 expression at its endogenous sites using an Imp-L2-Gal4 driver delays pupariation, while Imp-L2 mutants exhibit a slight acceleration of development. These effects are strongly enhanced by starvation and are accompanied by massive alterations of ecdysone production resulting most likely from increased Imp-L2 production by neurons directly contacting the PG and not from elevated Imp-L2 levels in the hemolymph. Taken together our results suggest that Imp-L2-expressing neurons sense the nutritional state of Drosophila larvae and coordinate dietary information and ecdysone production to adjust developmental timing under starvation conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries.

PubMed

Chen, Zhengju; Zhang, Xu; Ying, Lei; Dou, Dou; Li, Yanhui; Bai, Yun; Liu, Juan; Liu, Limei; Feng, Han; Yu, Xiaoxing; Leung, Susan Wai-Sum; Vanhoutte, Paul M; Gao, Yuansheng

2014-08-01

cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3',5'-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (Po2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5'-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK. Copyright © 2014 the American Physiological Society.

Imp and Syp RNA-binding proteins govern decommissioning of Drosophila neural stem cells

PubMed Central

Yang, Ching-Po; Samuels, Tamsin J.; Huang, Yaling; Yang, Lu; Ish-Horowicz, David; Davis, Ilan

2017-01-01

The termination of the proliferation of Drosophila neural stem cells, also known as neuroblasts (NBs), requires a ‘decommissioning’ phase that is controlled in a lineage-specific manner. Most NBs, with the exception of those of the mushroom body (MB), are decommissioned by the ecdysone receptor and mediator complex, causing them to shrink during metamorphosis, followed by nuclear accumulation of Prospero and cell cycle exit. Here, we demonstrate that the levels of Imp and Syp RNA-binding proteins regulate NB decommissioning. Descending Imp and ascending Syp expression have been shown to regulate neuronal temporal fate. We show that Imp levels decline slower in the MB than in other central brain NBs. MB NBs continue to express Imp into pupation, and the presence of Imp prevents decommissioning partly by inhibiting the mediator complex. Late-larval induction of transgenic Imp prevents many non-MB NBs from decommissioning in early pupae. Moreover, the presence of abundant Syp in aged NBs permits Prospero accumulation that, in turn, promotes cell cycle exit. Together, our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages. PMID:28851709

IMP-27, a Unique Metallo-β-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis.

PubMed

Dixon, Nyssa; Fowler, Randal C; Yoshizumi, A; Horiyama, Tsukasa; Ishii, Y; Harrison, Lucas; Geyer, Chelsie N; Moland, Ellen Smith; Thomson, Kenneth; Hanson, Nancy D

2016-10-01

A novel metallo-β-lactamase gene, blaIMP-27, was identified in unrelated Proteus mirabilis isolates from two geographically distinct locations in the United States. Both isolates harbor blaIMP-27 as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27. Copyright © 2016 Dixon et al.

13 CFR 123.19 - May I request an increase in the amount of an economic injury loan?

Code of Federal Regulations, 2010 CFR

2010-01-01

... amount of an economic injury loan? 123.19 Section 123.19 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Overview § 123.19 May I request an increase in the amount of an economic... increase is essential for your business to continue and is based on events occurring after SBA approved...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2012 CFR

2012-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

Code of Federal Regulations, 2011 CFR

2011-01-01

...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2011 CFR

2011-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

Code of Federal Regulations, 2012 CFR

2012-01-01

...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2010 CFR

2010-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

Code of Federal Regulations, 2014 CFR

2014-01-01

...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2013 CFR

2013-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.103 - What happens if I am forced to move from my home?

Code of Federal Regulations, 2014 CFR

2014-01-01

... move from my home? 123.103 Section 123.103 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.103 What happens if I am forced to move from my home? If... case, your loan would be an amount that SBA considers sufficient to replace your residence at your new...

13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

Code of Federal Regulations, 2013 CFR

2013-01-01

...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

Diffusion-weighted-preparation (D-prep) MRI as a future extension of SPECT/CT based surgical planning for sentinel node procedures in the head and neck area?

PubMed

Buckle, Tessa; KleinJan, Gijs H; Engelen, Thijs; van den Berg, Nynke S; DeRuiter, Marco C; van der Heide, Uulke; Valdes Olmos, Renato A; Webb, Andrew; van Buchem, Mark A; Balm, Alfons J; van Leeuwen, Fijs W B

2016-09-01

Even when guided by SPECT/CT planning of nodal resection in the head-and-neck area is challenging due to the many critical anatomical structures present within the surgical field. In this study the potential of a (SPECT/)MRI-based surgical planning method was explored. Hereby MRI increases the identification of SNs within clustered lymph nodes (LNs) and vital structures located adjacent to the SN (such as cranial nerve branches). SPECT/CT and pathology reports from 100 head-and-neck melanoma and 40 oral cavity cancer patients were retrospectively assessed for SN locations in levels I-V and degree of nodal clustering. A diffusion-weighted-preparation magnetic resonance neurography (MRN) sequence was used in eight healthy volunteers to detect LNs and peripheral nerves. In 15% of patients clustered nodes were retrospectively shown to be present at the location where the SN was identified on SPECT/CT (level IIA: 37.2%, level IIB: 21.6% and level III: 15.5%). With MRN, improved LN delineation enabled discrimination of individual LNs within a cluster. Uniquely, this MRI technology also provided insight in LN distribution (23.2±4 LNs per subject) and size (range 21-372mm(3)), and enabled non-invasive assessment of anatomical variances in the location of the LNs and facial nerves. Diffusion-weighted-preparation MRN enabled improved delineation of LNs and their surrounding delicate anatomical structures in the areas that most often harbor SNs in the head-and-neck. Based on our findings a combined SPECT/MRI approach is envisioned for future surgical planning of complex SN resections in this region. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incremental value of 99mTc-HYNIC-TOC SPECT/CT over whole-body planar scintigraphy and SPECT in patients with neuroendocrine tumours.

PubMed

Trogrlic, Mate; Težak, Stanko

2017-06-12

The aim of this study was to evaluate the additional value of 99m Tc-HYNIC-TOC SPECT/CT over planar whole-body (WB) scintigraphy and SPECT alone in the detection and accurate localisation of neuroendocrine tumour (NET) lesions. This study included 65 patients with a definitive histological diagnosis of NET prior to scintigraphy. Planar WB scintigraphy, SPECT, and SPECT/CT images were acquired at 4 h post-administration of 670 MBq 99m Tc-HYNIC-TOC. Additional SPECT images at 10 min after tracer administration were also acquired. Clinical and imaging follow-up findings were considered as the reference standards (minimum follow-up period, 15 months). Patient and lesion-based analyses of the efficacies of the imaging modalities were performed. While 38 patients exhibited metastasis of NETs, 27 presented no evidence of metastasis. Upon patient-based analysis, the sensitivity and specificity of SPECT/CT were found to be 88.9 and 79.3 %, respectively. The diagnostic accuracies of WB scintigraphy, 4h-SPECT, and SPECT/CT were 72.3, 73.8, and 84.6 %, respectively. The area under curve (AUC) value for SPECT/CT (0.84) was the highest, followed by those for 4h-SPECT (0.75) and WB scintigraphy (0.74). The accuracy and AUC values of SPECT/CT were significantly better compared to those of WB scintigraphy (p < 0.001), 10 min-SPECT (p < 0.001), and 4 h-SPECT (p = 0.001). The findings of SPECT/CT led to the change in treatment plan of 11 patients (16.9 %). The sensitivity and diagnostic accuracy of SPECT/CT in the evaluation of NET lesions outperforms planar WB imaging or SPECT alone.

Characterization of the Eimeria maxima sporozoite surface protein IMP1.

PubMed

Jenkins, M C; Fetterer, R; Miska, K; Tuo, W; Kwok, O; Dubey, J P

2015-07-30

The purpose of this study was to characterize Eimeria maxima immune-mapped protein 1 (IMP1) that is hypothesized to play a role in eliciting protective immunity against E. maxima infection in chickens. RT-PCR analysis of RNA from unsporulated and sporulating E. maxima oocysts revealed highest transcription levels at 6-12h of sporulation with a considerable downregulation thereafter. Alignment of IMP1 coding sequence from Houghton, Weybridge, and APU-1 strains of E. maxima revealed single nucleotide polymorphisms that in some instances led to amino acid changes in the encoded protein sequence. The E. maxima (APU-1) IMP1 cDNA sequence was cloned and expressed in 2 different polyHis Escherichia coli expression vectors. Regardless of expression vector, recombinant E. maxima IMP1 (rEmaxIMP1) was fairly unstable in non-denaturing buffer, which is consistent with stability analysis of the primary amino acid sequence. Antisera specific for rEmaxIMP1 identified a single 72 kDa protein or a 61 kDa protein by non-reducing or reducing SDS-PAGE/immunoblotting. Immunofluorescence staining with anti-rEmaxIMP1, revealed intense surface staining of E. maxima sporozoites, with negligible staining of merozoite stages. Immuno-histochemical staining of E. maxima-infected chicken intestinal tissue revealed staining of E. maxima developmental stages in the lamnia propia and crypts at both 24 and 48 h post-infection, and negligible staining thereafter. The expression of IMP1 during early stages of in vivo development and its location on the sporozoite surface may explain in part the immunoprotective effect of this protein against E. maxima infection. Published by Elsevier B.V.

Electrocardiograph-gated single photon emission computed tomography radionuclide angiography presents good interstudy reproducibility for the quantification of global systolic right ventricular function.

PubMed

Daou, Doumit; Coaguila, Carlos; Vilain, Didier

2007-05-01

Electrocardiograph-gated single photon emission computed tomography (SPECT) radionuclide angiography provides accurate measurement of right ventricular ejection fraction and end-diastolic and end-systolic volumes. In this study, we report the interstudy precision and reliability of SPECT radionuclide angiography for the measurement of global systolic right ventricular function using two, three-dimensional volume processing methods (SPECT-QBS, SPECT-35%). These were compared with equilibrium planar radionuclide angiography. Ten patients with chronic coronary artery disease having two SPECT and planar radionuclide angiography acquisitions were included. For the right ventricular ejection fraction, end-diastolic volume and end-systolic volume, the interstudy precision and reliability were better with SPECT-35% than with SPECT-QBS. The sample sizes needed to objectify a change in right ventricular volumes or ejection fraction were lower with SPECT-35% than with SPECT-QBS. The interstudy precision and reliability of SPECT-35% and SPECT-QBS for the right ventricle were better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography on the same population. SPECT-35% and SPECT-QBS present good interstudy precision and reliability for right ventricular function, with the results favouring the use of SPECT-35%. The results are better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography. They need to be confirmed in a larger population.

Hypoxic Vasospasm Mediated by cIMP: When Soluble Guanylyl Cyclase Turns Bad.

PubMed

Gao, Yuansheng; Chen, Zhengju; Leung, Susan W S; Vanhoutte, Paul M

2015-06-01

In a number of isolated blood vessel types, hypoxia causes an acute contraction that is dependent on the presence of nitric oxide and activation of soluble guanylyl cyclase. It is more pronounced when the preparations are constricted and is therefore termed hypoxic augmentation of vasoconstriction. This hypoxic response is accompanied by increases in the intracellular level of inosine 5'-triphosphate and in the synthesis of inosine 3',5'-cyclic monophosphate (cIMP) by soluble guanylyl cyclase. The administration of exogenous cIMP or inosine 5'-triphosphate causes augmented vasoconstriction to hypoxia. Furthermore, the vasoconstriction evoked by hypoxia and cIMP is associated with increased activity of Rho kinase (ROCK), indicating that cIMP may mediate the hypoxic effect by sensitizing the myofilaments to Ca through ROCK. Hypoxia is implicated in exaggerated vasoconstriction in the pathogenesis of coronary artery disease, myocardial infarction, hypertension, and stroke. The newly found role of cIMP may help to identify unique therapeutic targets for certain cardiovascular disorders.

Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors.

PubMed

Mattner, Filomena; Mardon, Karine; Loc'h, Christian; Katsifis, Andrew

2006-06-13

In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [(123)I]IZOL, bound to a single class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6 and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial-synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p<0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral organs and in the brain. [(123)I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites.

Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome.

PubMed

Kilgore, Mark R; McIlwain, Carrie A; Schmidt, Rodney A; Norquist, Barbara M; Swisher, Elizabeth M; Garcia, Rochelle L; Rendi, Mara H

2016-01-01

Endometrial carcinoma (EC) is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS). LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR) genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC) expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC). In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ) with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O). Pathologists must answer these questions: is patient ≤60 (yes/no), if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered), if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp) and postimplementation (PostImp) that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism ® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA). There were 147 patients who met criteria (29 PreImp and 118 PostImp). IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8%) cases did not get any IHC, but PostImp, only 4/118 (3.39%) were missed ( P = 0.0448). Of cases with IHC ordered, 60.0% (15/25) were ordered before or at S/O PreImp versus 91.2% (104/114) PostImp ( P = 0.0004). Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227), with the average being before S/O PostImp. This algorithm ensures MMR IHC ordering in women ≤60 with EC and can be applied to similar scenarios. Ancillary tests for management are increasing, especially genetic and molecular-based methods. The burden of managing orders and results remains with the pathologist and relying on human intervention alone is ineffective. Ordering IHC before or at S/O prevents oversight and the additional work of retrospective ordering and reporting.

Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.

PubMed

Chen, Chun-Jen; Bando, Kazunori; Ashino, Hiroki; Taguchi, Kazumi; Shiraishi, Hideaki; Fujimoto, Osuke; Kitamura, Chiemi; Matsushima, Satoshi; Fujinaga, Masayuki; Zhang, Ming-Rong; Kasahara, Hiroyuki; Minamizawa, Takao; Jiang, Cheng; Ono, Maiko; Higuchi, Makoto; Suhara, Tetsuya; Yamada, Kazutaka; Ji, Bin

2014-08-01

Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reliability and concurrent validity of the Infant Motor Profile.

PubMed

Heineman, Kirsten R; Middelburg, Karin J; Bos, Arend F; Eidhof, Lieke; La Bastide-Van Gemert, Sacha; Van Den Heuvel, Edwin R; Hadders-Algra, Mijna

2013-06-01

The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour in infancy. It consists of five domains: movement variation, variability, fluency, symmetry, and performance. The aim of this study was to assess interobserver reliability and concurrent validity of the IMP with the Alberta Infant Motor Scale (AIMS) and an age-specific neurological examination. Fifty-nine preterm infants (25 females, 34 males; median gestational age 29.7wks, median birthweight 1285g) and 146 term infants (74 females, 72 males; median gestational age 40.1wks, birthweight 3500g) were included. Assessments were performed at corrected ages of 4, 6, 10, 12, and 18 months and consisted of the IMP, AIMS, and an age-specific neurological examination. Interobserver reliability was investigated on a sample of 25 video recordings. Non-parametric statistics were used to analyse the data. Interobserver reliability was high (intraclass correlation coefficient 0.95). At all ages, AIMS scores correlated weakly to fairly with total IMP scores (Spearman's ρ 0.36-0.55), but moderately to strongly with scores on the performance domain of the IMP (Spearman's ρ 0.47-0.84). A clear relation was found between total IMP score and outcome of the neurological examination (Kruskal-Wallis p<0.001 at all ages). Interobserver reliability of the IMP is good. Concurrent validity with the AIMS is best for the IMP performance domain. Concurrent validity with age-specific neurological examination is very good. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Characterization of Protein Detergent Complexes by NMR, Light Scattering, and Analytical Ultracentrifugation

PubMed Central

Maslennikov, Innokentiy; Krupa, Martin; Dickson, Christopher; Esquivies, Luis; Blain, Katherine; Kefala, Georgia; Choe, Senyon; Kwiatkowski, Witek

2009-01-01

Bottlenecks in expression, solubilization, purification and crystallization hamper the structural study of integral membrane proteins (IMPs). Successful crystallization is critically dependent on the purity, stability and oligomeric homogeneity of an IMP sample. These characteristics are in turn strongly influenced by the type and concentration of the detergents used in IMP preparation. By utilizing the techniques and analytical tools we earlier developed for the characterization of protein-detergent complexes (PDCs) (Maslennikov et al., 2007), we demonstrate that for successful protein extraction from E. coli membrane fractions, the solubilizing detergent associates preferentially to IMPs rather than to membrane lipids. Notably, this result is contrary to the generally accepted mechanism of detergent-mediated IMP solubilization. We find that for one particular member of the family of proteins studied (E. coli receptor kinases, which is purified in mixed multimeric states and oligomerizes through its transmembrane region), the protein oligomeric composition is largely unaffected by a 10-fold increase in protein concentration, by alteration of micelle properties through addition of other detergents to the PDC sample, or by a 20-fold variation in the detergent concentration used for solubilization of the IMP from the membrane. We observed that the conditions used for expression of the IMP, which impact protein density in the membrane, has the greatest influence on the IMP oligomeric structure. Finally, we argue that for concentrating PDCs smaller than 30 kDa, stirred concentration cells are less prone to over-concentration of detergent and are therefore more effective than centrifugal ultrafiltration devices. PMID:19214777

Micro-scale NMR Experiments for Monitoring the Optimization of Membrane Protein Solutions for Structural Biology.

PubMed

Horst, Reto; Wüthrich, Kurt

2015-07-20

Reconstitution of integral membrane proteins (IMP) in aqueous solutions of detergent micelles has been extensively used in structural biology, using either X-ray crystallography or NMR in solution. Further progress could be achieved by establishing a rational basis for the selection of detergent and buffer conditions, since the stringent bottleneck that slows down the structural biology of IMPs is the preparation of diffracting crystals or concentrated solutions of stable isotope labeled IMPs. Here, we describe procedures to monitor the quality of aqueous solutions of [ 2 H, 15 N]-labeled IMPs reconstituted in detergent micelles. This approach has been developed for studies of β-barrel IMPs, where it was successfully applied for numerous NMR structure determinations, and it has also been adapted for use with α-helical IMPs, in particular GPCRs, in guiding crystallization trials and optimizing samples for NMR studies (Horst et al ., 2013). 2D [ 15 N, 1 H]-correlation maps are used as "fingerprints" to assess the foldedness of the IMP in solution. For promising samples, these "inexpensive" data are then supplemented with measurements of the translational and rotational diffusion coefficients, which give information on the shape and size of the IMP/detergent mixed micelles. Using microcoil equipment for these NMR experiments enables data collection with only micrograms of protein and detergent. This makes serial screens of variable solution conditions viable, enabling the optimization of parameters such as the detergent concentration, sample temperature, pH and the composition of the buffer.

Increased uptake of [123I]-meta-iodobenzylguanidine and [18F]-dopamine in mouse pheochromocytoma cells and tumors after treatment with the histone deacetylase inhibitors romidepsin and trichostatin A

PubMed Central

Martiniova, Lucia; Perera, Shiromi M.; Brouwers, Frederieke M.; Alesci, Salvatore; Abu-Asab, Mones; Marvelle, Amanda F.; Kiesewetter, Dale O.; Thomasson, David; Morris, John C.; Kvetnansky, Richard; Tischler, Arthur S.; Reynolds, James C; Fojo, A. Tito; Pacak, Karel

2014-01-01

Purpose [131I]-meta-iodobenzylguanidine ([131I]-MIBG) is the most commonly employed treatment for metastatic pheochromocytoma and paraganglioma; however, its success is limited. Its efficacy depends on the [131I]-MIBG concentration reached within the tumor through its uptake via the norepinephrine transporter and retention in neurosecretory granules. Purpose is to enhance [123I]-MIBG uptake in cells and liver pheochromocytoma tumors. Experimental Design We report the in vitro effects of two histone deacetylase (HDAC) inhibitors, romidepsin and trichostatin A, on increased uptake of [3H]-norepinephrine and [123I]-MIBG in mouse pheochromocytoma (MPC) cells, and the effect of romidepsin on [18F]-fluorodopamine and [123I]-MIBG uptake in a mouse model of metastatic pheochromocytoma. The effects of both inhibitors on norepinephrine transporter activity were assessed in MPC cells by [123I]-MIBG uptake studies with and without the transporter blocking agent desipramine and the vesicular blocking agent reserpine. Results Both HDAC inhibitors increased [3H]-norepinephrine, [123I]-MIBG, and [18F]-fluorodopamine uptake through the norepinephrine transporter in MPC cells. In vivo, inhibitor treatment resulted in increased uptake of [18F]-fluorodopamine and in pheochromocytoma liver metastases as measured by maximal standardized uptake values on PET imaging (p < 0.001). Analysis of biodistribution after inhibitor treatment confirmed the PET results in that uptake of [123I]-MIBG was significantly increased in liver metastases (p < 0.05). Therefore, HDAC inhibitor treatment increased radioisotope uptake in MPC cells in vitro and in liver metastases in vivo, through increased norepinephrine transporter activity. Conclusion These results suggest that HDAC inhibitors could enhance the therapeutic efficacy of [131I]-MIBG treatment in patients with malignant pheochromocytoma. PMID:21098082

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foss, Catherine A., E-mail: cfoss1@jhmi.edu; Bedja, Djahida; Faculty of Medicine and Health Sciences, Macquarie University, Sydney

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mousemore » model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.« less

SPECT/CT in patients with lower back pain after lumbar fusion surgery.

PubMed

Sumer, Johannes; Schmidt, Daniela; Ritt, Philipp; Lell, Michael; Forst, Raimund; Kuwert, Torsten; Richter, Richard

2013-10-01

The aim of the study was to investigate the incremental diagnostic value of skeletal hybrid imaging with single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) over conventional nuclear medical imaging in patients with lower back pain after lumbar fusion surgery (LFS). This retrospective study comprised 37 patients suffering from lower back pain after LFS in whom three-phase planar bone scintigraphies of the lumbar spine including SPECT/CT of that region had been performed. The findings visible on these imaging data sets were classified into the following five diagnostic categories: (a) metal loosening; (b) insufficient stabilizing function of the metal implants indicated by metabolically active facet joint arthritis and/or intervertebral osteochondrosis in the instrumented region; (c) adjacent instability defined as metabolically active degenerative disease in the segments adjacent to the instrumented region; (d) indeterminate; and (e) normal. In the case of eight patients no lesions were visible on their planar scintigraphy and SPECT (planar/SPECT) or SPECT/CT images. In the remaining 29 patients, planar/SPECT disclosed 62 pathological foci of uptake within the graft region and SPECT/CT revealed 55. The rate of reclassification by SPECT/CT compared with planar/SPECT was 5/12 for lesions categorized as metal loosening by planar/SPECT, 16/29 for foci with a planar/SPECT diagnosis of insufficient stabilizing function, 7/20 when the planar/SPECT diagnosis had been adjacent instability, and 1/1 for the lesions indeterminate on planar/SPECT. Two lesions had been detected on SPECT/CT only. The overall rate of reclassification was 45.2% (28/62) (95% confidence interval, 33.4-57.5%). Because of its significantly higher accuracy compared with planar/SPECT, SPECT/CT should be the conventional nuclear medical procedure of choice for patients with lower back pain after LFS.

Diagnostic accuracy and functional parameters of myocardial perfusion scintigraphy using accelerated cardiac acquisition with IQ SPECT technique in comparison to conventional imaging.

PubMed

Pirich, Christian; Keinrath, Peter; Barth, Gabriele; Rendl, Gundula; Rettenbacher, Lukas; Rodrigues, Margarida

2017-03-01

IQ SPECT consists of a new pinhole-like collimator, cardio-centric acquisition, and advanced 3D iterative SPECT reconstruction. The aim of this paper was to compare diagnostic accuracy and functional parameters obtained with IQ SPECT versus conventional SPECT in patients undergoing myocardial perfusion scintigraphy with adenosine stress and at rest. Eight patients with known or suspected coronary artery disease underwent [99mTc] tetrofosmin gated SPECT. Acquisition was performed on a Symbia T6 equipped with IQ SPECT and on a conventional gamma camera system. Gated SPECT data were used to calculate functional parameters. Scores analysis was performed on a 17-segment model. Coronary angiography and clinical follow-up were considered as diagnostic reference standard. Mean acquisition time was 4 minutes with IQ SPECT and 21 minutes with conventional SPECT. Agreement degree on the diagnostic accuracy between both systems was 0.97 for stress studies, 0.91 for rest studies and 0.96 for both studies. Perfusion abnormalities scores obtained by using IQ SPECT and conventional SPECT were not significant different: SSS, 9.7±8.8 and 10.1±6.4; SRS, 7.1±6.1 and 7.5±7.3; SDS, 4.0±6.1 and 3.9±4.3, respectively. However, a significant difference was found in functional parameters derived from IQ SPECT and conventional SPECT both after stress and at rest. Mean LVEF was 8% lower using IQ SPECT. Differences in LVEF were found in patients with normal LVEF and patients with reduced LVEF. Functional parameters using accelerated cardiac acquisition with IQ SPECT are significantly different to those obtained with conventional SPECT, while agreement for clinical interpretation of myocardial perfusion scintigraphy with both techniques is high.

Radioiodination and preclinical evaluation of 4-benzyl-1-(3-[125I]-iodobenzylsulfonyl)piperidine as a breast tumor imaging tracer in mouse.

PubMed

Sadeghzadeh, Masoud; Alirezapour, Behrouz; Charkhlooie, Ghorban Ali; Baghery, Maryam Keshavarz; Khorouti, Amir

2017-05-01

4-Benzyl-1-(3-iodobenzylsulfonyl)piperidine, 4-B-IBSP, has shown high-binding affinity to both sigma (σ) receptors in our previous work. In current study, radiolabeling and preclinical evaluation of 4-benzyl-1-(3-[ 125 I]-iodobenzylsulfonyl)piperidine, 4-B-[ 125 I]IBSP, in human ductal breast carcinoma (T47D) cells and in breast adenocarcinoma-bearing BALB/c mice are described. Radioiodination of this new σ ligand was performed by a palladium-catalyzed stannylation approach followed by oxidative iododestannylation reaction using Iodo-Gen. Competition-binding assays for binding of 4-B-[ 125 I]IBSP to guinea pig brain membranes and to T47D cells were performed with known σ ligands. The selectivity and binding characteristics (B max and K d ) were analyzed. In vitro stability and in vivo blood metabolism studies were also evaluated. Moreover, biodistribution studies were performed in normal and into the tumor-bearing mice at interval time points post-injection (p.i.). Both in vitro and in vivo blockade experiments were done in the presence of the σ receptors blocking agents. Radioiodinated ligand was obtained in high yield and high specific activity. The σ inhibition constants (K i , nM) for 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine (4-IBBSPz), (+)-pentazocine, haloperidol, DTG, and 4-B-IBSP were 1.37 ± 0.19, 3.90 ± 0.77, 2.69 ± 0.33, 30.62 ± 2.01, and 0.61 ± 0.05, respectively. 4-B-[ 125 I]IBSP bound to σ receptor sites preferably to very high-affinity binding sites on T47D cells. The radioligand showed acceptable in vitro and in vivo stabilities in the blood pool. However, in vivo biodistribution studies in normal Swiss albino mice revealed fast clearance of 4-B-[ 125 I]IBSP from blood and the other normal organs. Biodistribution experiments of 4-B-[ 125 I]IBSP in breast adenocarcinoma tumor-bearing BALB/c mice showed a relatively high tumor uptake at 30 min p.i. (4.13 ± 0.95) that reaches to 1.57 ± 0.24 even after 240 min p.i. A pre-injection of 4-B-IBSP and haloperidol with 4-B-[ 125 I]IBSP resulted in 36-57% decrease in activity in the tumor, liver, and brain at 60 min p.i. The high affinity of 4-B-[ 125 I]IBSP to σ receptor-binding sites, its relatively high uptake, and preferential retention in the tumor as well as an increasing trend observed in the tumor to blood and in the tumor to muscle ratios suggests that an iodine-123 labeled counterpart, 4-B-[ 123 I]IBSP, would be a promising σ radioligand for pursuing further studies to assess its potential for breast tumors imaging with SPECT.

13 CFR 123.15 - What if I change my mind?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false What if I change my mind? 123.15... § 123.15 What if I change my mind? If SBA required you to pledge collateral for your loan, you may change your mind and rescind your loan pursuant to the Consumer Credit Protection Act, 15 U.S.C. 1601...

13 CFR 123.15 - What if I change my mind?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false What if I change my mind? 123.15... § 123.15 What if I change my mind? If SBA required you to pledge collateral for your loan, you may change your mind and rescind your loan pursuant to the Consumer Credit Protection Act, 15 U.S.C. 1601...

13 CFR 123.15 - What if I change my mind?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false What if I change my mind? 123.15... § 123.15 What if I change my mind? If SBA required you to pledge collateral for your loan, you may change your mind and rescind your loan pursuant to the Consumer Credit Protection Act, 15 U.S.C. 1601...

13 CFR 123.15 - What if I change my mind?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What if I change my mind? 123.15... § 123.15 What if I change my mind? If SBA required you to pledge collateral for your loan, you may change your mind and rescind your loan pursuant to the Consumer Credit Protection Act, 15 U.S.C. 1601...

13 CFR 123.15 - What if I change my mind?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false What if I change my mind? 123.15... § 123.15 What if I change my mind? If SBA required you to pledge collateral for your loan, you may change your mind and rescind your loan pursuant to the Consumer Credit Protection Act, 15 U.S.C. 1601...

[Evaluation of crossing calibration of (123)I-MIBG H/M ration, with the IDW scatter correction method, on different gamma camera systems].

PubMed

Kittaka, Daisuke; Takase, Tadashi; Akiyama, Masayuki; Nakazawa, Yasuo; Shinozuka, Akira; Shirai, Muneaki

2011-01-01

(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.

Diagnostic role of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases.

PubMed

Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

2014-01-01

The bone metastasis appeared early before the bone imaging for most of the above patients. (99)Tc(m)-MDP ((99)Tc(m) marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi (99)Tc(m)-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

Assessment of myocardial viability using 123I-labeled iodophenylpentadecanoic acid at sustained low flow or after acute infarction and reperfusion.

PubMed

Yang, J Y; Ruiz, M; Calnon, D A; Watson, D D; Beller, G A; Glover, D K

1999-05-01

123I-labeled iodophenylpentadecanoic acid (IPPA) is a synthetic fatty acid that may be useful for determination of myocardial viability. We investigated the uptake and clearance kinetics of this tracer in canine models of ischemia and infarction. In protocol 1, 185 MBq (5 mCi) 123I-IPPA were injected intravenously in 19 dogs with 50% left anterior descending artery (LAD) flow reduction. In 9 dogs, 201TI was coinjected. In protocol 2, 5 dogs underwent LAD occlusion for 3 h, and 123I-IPPA was injected 60 min after reperfusion. All dogs had flow measured by microspheres, regional systolic thickening by ultrasonic crystals and measurements of postmortem risk area and infarct size. Tracer activities were quantified by gamma well counting and by serial imaging. In protocol 1 dogs with sustained low flow (50% +/- 4%) and absence of systolic thickening (-3.2% +/- 1%), 123I-IPPA defect magnitude (LAD/left circumflex artery [LCX] count ratios) decreased from 0.65 +/- 0.02 to 0.74 +/- 0.02 at 30 min and to 0.84 +/- 0.03 at 2 h (P < 0.01), indicative of rest redistribution. Final transmural 123I-IPPA LAD/LCX activity ratio (0.99 +/- 0.05) was significantly greater than the flow ratio (0.53 +/- 0.04) at injection, confirming complete rest redistribution. The final 123I-IPPA activity ratio was significantly greater than the 201TI ratio over the 2-h period (P < 0.01). In protocol 2 dogs that underwent 3 h of total LAD occlusion and reflow (infarct size = 51% +/- 13% of risk area), viability was overestimated with 123I-IPPA, because uptake averaged 64% of normal in the central necrotic region, where flow averaged < 10% of normal. These findings suggest that serial 123I-IPPA imaging may be useful for assessing myocardial viability under conditions of sustained low flow and myocardial asynergy, such as appears to exist in patients with chronic coronary artery disease and depressed left ventricular function. In contrast, 123I-IPPA given early after reperfusion following prolonged coronary occlusion overestimates the degree of viability and therefore may not provide useful information pertaining to the degree of myocardial salvage after reflow in the setting of acute myocardial infarction.

IQ-SPECT for thallium-201 myocardial perfusion imaging: effect of normal databases on quantification.

PubMed

Konishi, Takahiro; Nakajima, Kenichi; Okuda, Koichi; Yoneyama, Hiroto; Matsuo, Shinro; Shibutani, Takayuki; Onoguchi, Masahisa; Kinuya, Seigo

2017-07-01

Although IQ-single-photon emission computed tomography (SPECT) provides rapid acquisition and attenuation-corrected images, the unique technology may create characteristic distribution different from the conventional imaging. This study aimed to compare the diagnostic performance of IQ-SPECT using Japanese normal databases (NDBs) with that of the conventional SPECT for thallium-201 ( 201 Tl) myocardial perfusion imaging (MPI). A total of 36 patients underwent 1-day 201 Tl adenosine stress-rest MPI. Images were acquired with IQ-SPECT at approximately one-quarter of the standard time of conventional SPECT. Projection data acquired with the IQ-SPECT system were reconstructed via an ordered subset conjugate gradient minimizer method with or without scatter and attenuation correction (SCAC). Projection data obtained using the conventional SPECT were reconstructed via a filtered back projection method without SCAC. The summed stress score (SSS) was calculated using NDBs created by the Japanese Society of Nuclear Medicine working group, and scores were compared between IQ-SPECT and conventional SPECT using the acquisition condition-matched NDBs. The diagnostic performance of the methods for the detection of coronary artery disease was also compared. SSSs were 6.6 ± 8.2 for the conventional SPECT, 6.6 ± 9.4 for IQ-SPECT without SCAC, and 6.5 ± 9.7 for IQ-SPECT with SCAC (p = n.s. for each comparison). The SSS showed a strong positive correlation between conventional SPECT and IQ-SPECT (r = 0.921 and p < 0.0001), and the correlation between IQ-SPECT with and without SCAC was also good (r = 0.907 and p < 0.0001). Regarding diagnostic performance, the sensitivity, specificity, and accuracy were 80.8, 78.9, and 79.4%, respectively, for the conventional SPECT; 80.8, 80.3, and 82.0%, respectively, for IQ-SPECT without SCAC; and 88.5, 86.8, and 87.3%, respectively, for IQ-SPECT with SCAC, respectively. The area under the curve obtained via receiver operating characteristic analysis were 0.77, 0.80, and 0.86 for conventional SPECT, IQ-SPECT without SCAC, and IQ-SPECT with SCAC, respectively (p = n.s. for each comparison). When appropriate NDBs were used, the diagnostic performance of 201 Tl IQ-SPECT was comparable with that of the conventional system regardless of different characteristics of myocardial accumulation in the conventional system.

IMPS, A Static-Optics Application of Full-Stokes Spectropolarimetry to Search for Extraterrestrial Biosignatures

NASA Astrophysics Data System (ADS)

Telesco, C. M.; Sparks, W. B.; Zhao, B.; Varosi, F.; Schofield, S.; Germer, T. A.; Kolokolova, L.; Parenteau, M. N.; Cooper, G.; Grundy, W. M.; Guzmán, R.; Pantin, E.

2016-12-01

Optical spectropolarimetry holds great promise in the search for extraterrestrial life. In particular, the detection of circular polarization can indicate chirality, a signature of biological significance. We describe an on-going effort to implement the full-Stokes (I, Q, U, V), static-optics concept for optical spectropolarimetry described by Sparks et al. [App. Optics, 51, 5495 (2012)]. Our early breadboard embodiments of the concept demonstrate its simplicity and indicate its potential for space missions in which a compact design with no moving parts is crucial to achieve the mission goals. We describe the instrument, called the Integrated Miniature Polarimeter and Spectrograph (IMPS), and consider one example for its deployment: a mission to land on an outer solar system body such as Europa.

Objective evaluation of reconstruction methods for quantitative SPECT imaging in the absence of ground truth.

PubMed

Jha, Abhinav K; Song, Na; Caffo, Brian; Frey, Eric C

2015-04-13

Quantitative single-photon emission computed tomography (SPECT) imaging is emerging as an important tool in clinical studies and biomedical research. There is thus a need for optimization and evaluation of systems and algorithms that are being developed for quantitative SPECT imaging. An appropriate objective method to evaluate these systems is by comparing their performance in the end task that is required in quantitative SPECT imaging, such as estimating the mean activity concentration in a volume of interest (VOI) in a patient image. This objective evaluation can be performed if the true value of the estimated parameter is known, i.e. we have a gold standard. However, very rarely is this gold standard known in human studies. Thus, no-gold-standard techniques to optimize and evaluate systems and algorithms in the absence of gold standard are required. In this work, we developed a no-gold-standard technique to objectively evaluate reconstruction methods used in quantitative SPECT when the parameter to be estimated is the mean activity concentration in a VOI. We studied the performance of the technique with realistic simulated image data generated from an object database consisting of five phantom anatomies with all possible combinations of five sets of organ uptakes, where each anatomy consisted of eight different organ VOIs. Results indicate that the method provided accurate ranking of the reconstruction methods. We also demonstrated the application of consistency checks to test the no-gold-standard output.

Tumor Localization and Biochemical Response to Cure in Tumor-Induced Osteomalacia

PubMed Central

Chong, William H.; Andreopoulou, Panagiota; Chen, Clara C.; Reynolds, James; Guthrie, Lori; Kelly, Marilyn; Gafni, Rachel I.; Bhattacharyya, Nisan; Boyce, Alison M.; El-Maouche, Diala; Crespo, Diana Ovejero; Sherry, Richard; Chang, Richard; Wodajo, Felasfa M.; Kletter, Gad B.; Dwyer, Andrew; Collins, Michael T.

2013-01-01

Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and post-operative biochemical changes in 31 subjects with TIO. All had failed either initial, or re-localization (in case of recurrence or metastases at outside institutions). Functional imaging with 111Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and 18fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT,MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20/31 subjects (64.5%). Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16/20 FDG-PET/CT imaging. Eighteen of 19 (95%) were positive on octreo-SPECT, and 14/16 (88%) on FDG-PET/CT. Twelve of 20 subjects underwent VS; 10/12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were: sensitivity=0.95, specificity=0.64, PPV=0.82 and NPV=0.88 for octreo-SPECT; sensitivity=0.88, specificity=0.36, PPV=0.62 and NPV=0.50 for FDG-PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up. Serum phosphorus returned to normal in all subjects within 1-5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25-dihydroxyvitamin D3 (1,25D) rose and exceeded the normal range. In this systematic approach to TIO tumor localization Octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation. PMID:23362135

IMP 7 (Explorer 47) trajectory, September 26, 1972 to September 25, 1978

NASA Technical Reports Server (NTRS)

Milligan, Pamela A.; Lazarus, Alan J.

1988-01-01

The trajectory plots for IMP 7 (Explorer 47) are contained. For each orbit the trajectory is shown in five panels on two pages; each panel is a different representation or projection. The trajectory parameters were obtained from the multi-coordinate ephemeris (MCE) tapes supplied to IMP experimenters by the IMP project. The plots on the right hand pages use a geocentric, solar-ecliptic coordinate system. Distances are in units of earth radii. The plots on the left hand pages use geocentric, solar magnetospheric coordinates with distances in earth radii.

Imp2 regulates GBM progression by activating IGF2/PI3K/Akt pathway.

PubMed

Mu, Qingchun; Wang, Lijun; Yu, Fengbo; Gao, Haijun; Lei, Ting; Li, Peiwen; Liu, Pengfei; Zheng, Xu; Hu, Xitong; Chen, Yong; Jiang, Zhenfeng; Sayari, Arash J; Shen, Jia; Huang, Haiyan

2015-01-01

Glioblastomas multiforme (GBM) are the most frequently occurring malignant brain cancers. Treatment for GBM consists of surgical resection and subsequent adjuvant radiation therapy and chemotherapy. Despite this, GBM patient survival is limited to 12-15 months, and researchers are continually trying to develop improved therapy options. Insulin-like growth factor 2 mRNA-binding protein 2 (Imp2) is known to be upregulated in many cancers and is known to regulate the signaling activity of insulin-like growth factor 2 (IGF2). However, relatively little is known about its role in malignant development of GBM. In this study, we first found Imp2 is upregulated in GBM tissues by using clinical samples and public database search. Studies with loss and gain of Imp2 expression in in vitro GBM cell culture system demonstrated the role of Imp2 in promoting GBM cell proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT). Additionally, our results show that Imp2 regulates the activity of IGF2, which further activates PI3K/Akt signaling, thereby to promote GBM malignancy. Inhibition of Imp2 was also found to sensitize GBM to temozolomide treatment. These observations add to the current knowledge of GBM biology, and may prove useful in development of more effective GBM therapy.