Anatomically standardised <Superscript>99m</Superscript>Tc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers,multiple system atrophy and idiopathic Parkinson's disease

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6+/-10.2 years; disease duration 11.0+/-6.4 years; 50 males/31 females), 15 MSA patients (61.5+/-9.2 years; disease duration 3.0+/-2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2+/-11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers) resulted in an overall accuracy of 86% post hoc, with 98% of normals, 78% of IPD and 93% of MSA correctly classified. These values were slightly lower after cross-validation: 96% for healthy volunteers, 77% for IPD and 67% for MSA. In conclusion, using age- and gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between IPD and MSA with high discriminating power in clinically relevant circumstances.     

Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis.

Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET). METHODS: One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique. RESULTS: Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV). CONCLUSION: Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.     

Quantitative simultaneous 99mTc-ECD/123I-FP-CIT SPECT in Parkinson’s disease and multiple system atrophy

Purpose The purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinsons disease (IPD) and multiple system atrophy (MSA).Methods Simultaneous ^99mTc-ECD/¹²³I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus.Results Striatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p<0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p<0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p<0.05).Conclusion Dual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes.     

Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease.

(E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with (123)I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed (123)I-PE2I SPECT on healthy volunteers and patients with Parkinson's disease (PD) to validate the Logan graphical method for quantification of (123)I-PE2I binding and to analyze the relationship between (123)I-PE2I SPECT and clinical features of this frequent degenerative disease. METHODS: Eight PD patients (3 women, 5 men; mean age, 64 +/- 7.9 y; disease duration range, 1-8 y, Hoehn and Yahr stage range, 1-2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 +/- 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 +/- 30 MBq of (123)I-PE2I. RESULTS: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. (123)I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, (123)I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, (123)I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that (123)I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. CONCLUSION: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that (123)I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that (123)I-PE2I SPECT can be used for preclinical and early diagnosis of PD.     

Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET

Idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are the most common movement disorders associated with neurodegenerative disease. A clinical differential diagnosis of IPD and atypical Parkinsonian disorders, such as MSA and PSP, is often complicated by the presence of symptoms common to both groups. Since Parkinsonism has a different pathophysiology in the cortical and subcortical brain structures, assessing the regional cerebral glucose metabolism may assist in making a differential diagnosis of Parkinsonism. The 18F-FDG PET images of IPD, MSA and PSP were assessed using statistical parametric mapping (SPM) in order to determine the useful metabolic patterns. Twenty-four patients with Parkinsonism: eight patients (mean age 67.9 +/- 10.7 years; M/F: 3/5) with IPD, nine patients (57.9 +/- 9.2 years; M/F: 4/5) with MSA and seven patients (67.6 +/- 4.8 years; M/F: 3/4) with PSP were enrolled in this study. All patients with Parkinsonism and 22 age-matched normal controls underwent 18F-FDG PET, (after 370 MBq 18F-FDG). The three groups and the individual IPD, MSA and PSP patients were compared with a normal control group using a two-sided t-test of SPM (uncorrected P < 0.01, extent threshold > 100 voxel). The IPD, MSA and PSP groups showed significant hypometabolism in the cerebral neocortex compared to the normal control group. The MSA group showed significant hypometabolism in the putamen, pons and cerebellum compared to the normal controls and IPD groups. In addition, PSP showed significant hypometabolism in the caudate nucleus, the thalamus, midbrain and the cingulate gyrus compared to the normal controls, the IPD and the MSA groups. In conclusion, an assessment of the 18F-FDG PET images using SPM may be a useful adjunct to a clinical examination when making a differential diagnosis of Parkinsonism.     

Changes in regional cerebral blood flow caused by deep-brain stimulation of the subthalamic nucleus in Parkinson's disease.

The aim of this study was to investigate the effect of deep-brain stimulation of the subthalamic nucleus (STN) on regional cerebral blood flow (rCBF) throughout the entire brain volume in patients with Parkinson's disease and to evaluate which of the brain areas showing an rCBF increase during STN stimulation related significantly to the improvement in motor function. METHODS: Ten consecutive Parkinson's disease patients (6 men, 4 women; mean age +/- SD, 59 +/- 8 y) with bilateral STN stimulators underwent 3 rCBF SPECT examinations at rest: the first preoperatively and the second and third postoperatively (follow-up, 4.8 +/- 1.4 mo) with STN stimulators on and off, respectively. The motor unified Parkinson's disease rating scale, the Hoehn and Yahr disability scale, and the Schwab and England activities-of-daily-living scale were used to evaluate the clinical state under each condition. Statistical parametric mapping was used to investigate rCBF during STN stimulation in comparison with rCBF preoperatively and with STN stimulators off. Also evaluated with statistical parametric mapping was the relationship between rCBF and individual motor scores used as covariates of interest. RESULTS: STN stimulation significantly changed rCBF in the right pre-supplementary motor area (pre-SMA), anterior cingulate cortex, and dorsolateral prefrontal cortex and in the medial Brodmann's area 8 (BA8) as defined in the atlas of Talairach and Tournoux (P < 0.05 corrected for multiple comparisons). The rCBF in these areas increased from the preoperative condition to the stimulators-on condition and decreased again after the stimulators were switched off. A significant correlation was detected between the improvement in motor scores and the rCBF increase only in the right pre-SMA and in the anterior cingulate motor area (P < 0.005, uncorrected). CONCLUSION: According to the topographic organization of the primate STN, our study shows that stimulation of the STN leads to rCBF increases in the motor (pre-SMA), associative, and limbic territories (anterior cingulate) in the frontal cortex. The significant correlation between motor improvement and rCBF increase in the pre-SMA and the anterior cingulate motor area reinforces the hypothesis that STN stimulation in parkinsonian patients can potentiate the cortical areas participating in higher-order aspects of motor control.     

Improved detection of left main coronary artery disease with attenuation-corrected SPECT

BACKGROUND: Myocardial perfusion imaging has demonstrated a limited sensitivity as a means of accurately identifying left main (LM) coronary disease. Because regional quantitative perfusion biases are eliminated with attenuation corrected (AC) single photon emission computed tomography (SPECT), as compared with uncorrected (NC) SPECT, we hypothesized that AC SPECT would demonstrate increased diagnostic accuracy for the detection of significant LM coronary stenosis. METHODS AND RESULTS: We studied 28 patients (23 men, 5 women; mean age, 66+/-9 years) with significant LM stenoses (> or =50%) and 34 control patients (27 men, 7 women; mean age, 65+/-11 years) with 2-vessel coronary disease. Rest thallium-201 and stress technetium 99m sestamibi SPECT imaging with and without AC were performed, as described earlier. Both AC and NC images were analyzed visually and quantitatively in comparison with corresponding normal databases. A greater sensitivity for detection of an LM defect pattern (64% vs. 7%, P = .0009) with equivalent specificity (94% vs. 100%, P = not significant) was demonstrated by means of visual analysis of AC SPECT images. More disease was demonstrated in a greater number of territories with AC SPECT images than with NC images (2.14+/-0.97 for AC images vs. 1.43+/-0.84 for NC images, P = .0001). Similar improvement in the detection of LM disease was shown by means of automated quantitative analysis (57% for AC SPECT vs 14% for NC SPECT, P = .0005), again with no loss in specificity. CONCLUSIONS: AC SPECT with the University of Michigan method in consecutive patients with LM stenoses and a select control population with severity matched multivessel coronary disease significantly improved the diagnostic accuracy of myocardial perfusion imaging for the identification of LM coronary disease, compared with uncorrected SPECT.     

Normal patterns on 99mTc-ECD brain SPECT scans in adults.

Normative ethyl cysteinate dimer (ECD) SPECT data must be available to successfully apply ECD SPECT to clinical studies. The purpose of this study was to determine ECD SPECT scan patterns of healthy adults. METHODS: Forty-eight healthy volunteers (22 men, 26 women; age range, 22-95 y; mean age, 47.6 +/- 19.2 y) underwent high-resolution ECD SPECT. For visual analysis of regional brain ECD uptake, we used a scale of +3 to -3, in which +3 and -3 indicated highest ECD uptake and deficit, respectively. For quantitative analysis, we measured the region-to-cerebellum ratio (R/CE) and the region-to-cerebral cortex ratio (R/CO) for 17 regions (13 cortical, 3 subcortical, and 1 cerebellar). RESULTS: On visual analysis, no subject had a score of -3. All subjects had a score of -2 for the hippocampus and a score of +3 for the medial occipital cortex, except for 2 subjects who had a score of +3 for the striatum and thalamus. A frontal eye field and posterior parieto-occipital junction were identified in 60% of subjects with a score of +1 and 79% of subjects with a score of +2. On quantitative analysis, a significant regional variation (ANOVA, P < 0.0001) was seen in R/CE, ranging from 0.709 (hippocampus) to 1.26 (medial occipital cortex). However, regional right-to-left differences and intersubject variability of R/CE were small (asymmetry index, 3.6% +/- 0.8%; coefficient variation, 6.6% +/- 0.7%). R/CE declined significantly with age in 6 regions, including the anterior and posterior cingulate cortex, superior prefrontal and parietal cortex, striatum, and hippocampus (1.0%-2.0% per decade, P < 0.05), whereas R/CO in the cerebellum increased significantly with age (1.0% per decade, P < 0.05). CONCLUSION: Although regional ECD brain perfusion patterns vary significantly, including variability caused by the age-related effect, intersubject variability is small. Recognition of these normal patterns is important for clinical interpretation of ECD SPECT studies.     

Subcortical aphasia after striatocapsular infarction: quantitative analysis of brain perfusion SPECT using statistical parametric mapping and a statistical probabilistic anatomic map.

This study examined the relationship between the severity of aphasia and regional cerebral perfusion on brain SPECT using statistical parametric mapping (SPM) and a statistical probabilistic anatomic map (SPAM) in patients with a striatocapsular infarction (SCI) along with the other clinical and imaging findings. METHODS: The subjects were 16 right-handed Korean-speaking patients with a left SCI who underwent 99mTc-ethylcyteinate dimer (99mTc-ECD) SPECT (8.1 +/- 4.8 d [mean +/- SD] after onset). MRI showed that no patient had any abnormality in the cerebral cortex (6.8 +/- 6.0 d after onset). The aphasia quotient (AQ), which is a measure of the severity of aphasia, was obtained by using the Korean version of the Western Aphasia Battery (5.3 +/- 3.9 d after onset). For quantitative evaluation of cerebral perfusion, the asymmetry indices (AIs) for subcortical and cortical areas were calculated using SPM and SPAM. The infarct size was measured using MRI. RESULTS: Aphasia occurred in 15 (2 global, 7 transcortical, and 6 anomic aphasia) of the 16 patients. Left cerebral cortical hypoperfusion was observed in all 15 patients with subcortical aphasia. Aphasia was more severe in 6 patients with extensive cerebral cortical hypoperfusion than in the remaining 10 patients (AQ = 41.8 +/- 25.2 points vs. 84.2 +/- 7.7 points [mean +/- SD], P = 0.001). There was an association between the AQ and age (rho = -0.665), infarct size (rho = -0.594), AIs of the frontal cortex (rho = -0.653), temporal cortex (rho = -0.782), parietal cortex (rho = -0.694), whole cerebral cortex (rho = -0.768), and the cerebellar cortex (rho = 0.765). Voxel-based SPM analysis showed a significant positive correlation between the AQ and the perfusion of the left temporal cortex and the right cerebellum. CONCLUSION: The severity of subcortical aphasia after a left SCI without cortical abnormalities on MRI is associated with the extent and severity of the left cerebral cortical hypoperfusion on brain perfusion SPECT performed during the subacute stage, particularly in the left temporal cortex. Quantitative brain perfusion SPECT using SPM and SPAM can help in evaluating subcortical aphasia in a SCI because it provides functional information that cannot be obtained by morphologic imaging.     

Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience

PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS: The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group. CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.     

Imaging of dopamine transporters and D<Subscript>2</Subscript> receptors in patients with Parkinson’s disease and multiple system atrophy

Purpose The aim of this study was to ascertain whether combined presynaptic and postsynaptic dopaminergic single-photon emission computed tomography (SPECT) scanning is useful for differentiation between patients with idiopathic Parkinsons disease (IPD), patients with multiple system atrophy of the striatonigral type (MSA) and healthy subjects.Methods SPECT measurements of the dopamine transporter (DAT) were done with ¹²³I--CIT, while for determination of the dopamine D₂-like receptors (D₂), ¹²³I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight patients with MSA and 11 healthy age-matched control subjects.Results Putaminal DAT binding was reduced to 32% of control values in IPD and to 19% of control values in MSA . Significantly higher striatal asymmetry in DAT binding was found in MSA than in controls, but IPD patients had significantly higher asymmetry than MSA patients. Striatal D₂ binding did not differ significantly between patients and healthy controls but the ratio between caudate DAT and D₂ binding was significantly higher in patients with IPD than in those with MSA, even when disease severity was taken into account.Conclusion Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference greater than 15% are likely to suffer from IPD. Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference of between 5% and 15% are more likely to have MSA. ¹²³I-epidepride SPECT measurements may add further diagnostic information, since the ratio between DAT and D₂ receptor binding is significantly higher in IPD than in MSA.     

Evaluation of probable or possible dementia with lewy bodies using 123I-IMP brain perfusion SPECT, 123I-MIBG, and 99mTc-MIBI myocardial SPECT.

We evaluated the diagnostic usefulness of combination studies with a statistical mapping method in N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) brain perfusion SPECT, cardiac sympathetic nerve function by (123)I-metaiodobenzylguanidine ((123)I-MIBG), and myocardial function by electrocardiographically gated (99m)Tc-sestamibi ((99m)Tc-MIBI) SPECT for patients with probable or possible dementia with Lewy bodies (DLB). METHODS: Twelve patients with probable DLB (7 male, 5 female; mean age +/- SD, 72.3 +/- 5.63 y; range, 65-82 y) and 9 patients with possible DLB (3 male, 6 female; mean age +/- SD, 73.1 +/- 9.23 y; range, 59-88 y) were enrolled in this study. (123)I-IMP SPECT images were analyzed with 3-dimensional stereotactic surface projections (3D-SSP) and the severity of ischemia was classified objectively using quantitatively analytic and display software; stereotactic extraction estimation (SEE) methods were compared with a normal database. In addition, we evaluated (123)I-MIBG heart-to-mediastinum (H/M) uptake ratios. Moreover, we performed (99m)Tc-MIBI SPECT to evaluate myocardial perfusion and the left ventricular ejection fraction (LVEF) compared with a normal database. RESULTS: 3D-SSP images of group comparison with healthy control subjects showed significantly decreased perfusion in the parietotemporal, occipital cortex, posterior cingulated, and precuneus regions in the probable DLB group but no significant reduction in the possible DLB group. Mean H/M ratios in the probable DLB group were significantly lower than those of the possible DLB group and the control group, respectively. Ten of 12 patients (83.3%) with probable DLB and 1 of 9 patients (11.1%) with possible DLB showed severe reduction in the bilateral occipital lobe and also a low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 2 patients (22.2%) with possible DLB showed no bilateral occipital hypoperfusion but showed low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 6 patients (66.7%) with possible DLB showed no occipital hypoperfusion and normal (123)I-MIBG uptake. (99m)Tc-MIBI gated SPECT did not indicate any wall motion abnormality in any subjects. CONCLUSION: These results suggest that combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with (123)I-MIBG, would be a useful supporting diagnostic method in patients with DLB-particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion.     

Decreased dopamine transporter binding in Machado-Joseph disease.

The aim of this study was to use 99mTc-TRODAT-1 brain SPECT for investigation of the binding of dopamine transporter (DAT) in the nigrostriatal dopaminergic pathway of symptomatic Machado-Joseph disease (MJD) and to compare the results with the abnormal cytidylate, adenylate, and guanylate (CAG) expansion in the MJD1 gene and other clinical factors. METHODS: Ten symptomatic MJD patients (8 women, 2 men; age range, 20-71 y; mean age +/- SD, 36.4 +/- 10.6 y; mean duration of illness, 9.8 +/- 5.4 y) and 21 healthy volunteers (age range, 24-71 y; mean age, 47.6 +/- 20.1 y) were examined. Brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific nigrostriatal 99mTc-TRODAT-1 binding was measured and compared with the clinical symptoms, duration of illness, and size of abnormal expanded CAG repeats. RESULTS: All nigrostriatal 99mTc-TRODAT-1 ratios were significantly lower in MJD patients than in healthy volunteers (P < 0.05). Discriminant function analysis of all MJD patients showed that the decreased binding of 99mTc-TRODAT-1 in the putamen was not significantly different from that in the caudate nucleus. Eight of 10 MJD patients had significantly decreased 99mTc-TRODAT-1 uptake. Of these 8, 2 had extrapyramidal signs and 6 had no obvious extrapyramidal signs. The other 2 patients, who had normal 99mTc-TRODAT-1 uptake, had no obvious extrapyramidal signs. CONCLUSION: Our findings indicate that 99mTc-TRODAT-1 brain SPECT is an appropriate method for evaluating damage to the nigrostriatal DAT in symptomatic MJD patients with and without extrapyramidal signs. The decreased binding of 99mTc-TRODAT-1 in the nigrostriatal dopaminergic pathway in symptomatic MJD patients correlates with the phenotype of extrapyramidal signs but not with the abnormal CAG repeat length, age at disease onset, or disease duration.     

Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson's disease and multiple system atrophy

We explored if magnetic resonance imaging sequences might aid in the clinical differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). We measured the volumes of the olfactory bulb, the olfactory tract, and olfaction-associated cortical gray matter in 20 IPD patients, 14 MSA patients, and 12 normal subjects, using high-resolution magnetic resonance imaging sequences in combination with voxel-based statistical analysis. We found that, compared to normal subjects and MSA patients, the volumes of the olfactory bulb and tract were significantly reduced in IPD patients. The gray matter volume of IPD patients decreased in the following order: the olfactory area to the right of the piriform cortex, the right amygdala, the left entorhinal cortex, and the left occipital lobe. Further, the total olfactory bulb volume of IPD patients was associated with the duration of disease. The entorhinal cortical gray matter volume was negatively associated with the UPDRS III score.     

Lower accuracy of Tl-201 SPECT in women is not improved by size-based normal databases or Wiener filtering

BACKGROUND: We have shown that the diagnostic accuracy of quantitative single photon emission computed tomography (SPECT) thallium 201 myocardial perfusion imaging is lower in women than in men and that much of the difference can be explained by the smaller size of the left ventricle in women. Therefore attempts at improving the accuracy of myocardial perfusion imaging in women should focus on the problem of lower accuracy in patients with small chamber size. We evaluated two strategies for this: size- and gender-based normal databases and inverse filtering with the Wiener filter. METHODS AND RESULTS: We identified 618 patients undergoing exercise SPECT TI-201 who either had a low pre-test probability of coronary artery disease or had catheterization-documented disease. Their images were analyzed on the basis of gender and chamber size: both gender and size- and gender-based normal databases were created. The studies were analyzed quantitatively, and the accuracy was evaluated by use of the area under the receiver operating characteristic (ROC) curve. Chamber size was significantly lower in women (size index 69+/-22 women vs 96+/-28 men; P < .0001). The accuracy of myocardial perfusion imaging was lower in women compared with men (ROC area: 0.92+/-0.01 men vs 0.85+/-0.03 women; P = .03), and there was an even greater difference in accuracy between patients with large versus small chamber size (ROC area: 0.94+/-0.01 large vs 0.81+/-0.03 small; P < .001). There was no improvement in the diagnostic accuracy either in women or in patients with small chamber size when a size- and gender-based normal database, Wiener filter, or the Wiener filter with a size- and gender-based normal database was used. CONCLUSION: The left ventricular chamber size in women is smaller than that in men. There is a significant difference in the accuracy of quantitative SPECT TI-201 between men and women and an even greater difference between patients with large versus small chamber size. Neither size- and gender-based databases nor Wiener filtering significantly improves accuracy in women or in patients with small chamber size.     

Cerebral palsy: initial experience with Tc-99m HMPAO SPECT of the brain

The outlook for children with cerebral palsy is determined by the severity of motor problems and the presence of associated disabilities, in which early detection remains a medical challenge. The authors studied 13 children (aged 13 months to 12 years) with cerebral palsy by means of single photon emission computed tomography (SPECT) of the brain with technetium-99m hexamethylpropyleneamineoxime (HMPAO). In all children with hemiplegia, SPECT demonstrated hypoperfusion in the hemisphere contralateral to the motor deficit. SPECT demonstrated normal findings in patients with mild diplegia; bilateral hypoperfusion in the superior motor cortex in patients with moderate di- or tetraplegia; and bilateral reduction of perfusion in the superior motor, inferior motor, prefrontal, and parietal cortices in patients with severe di- or tetraplegia. Results suggest that Tc-99m HMPAO SPECT of the brain is a valuable complementary tool for thorough neurologic assessment in cerebral palsy.     

Differential diagnosis of Parkinson's disease and vascular parkinsonism by (99m)Tc-TRODAT-1.

The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Parkinson's disease. METHODS: Fourteen VP patients (age range, 59-87 y; mean age, 70 +/- 7.5 y), 30 Parkinson's disease patients (age range, 54-84 y; mean age, 65 +/- 8.8 y), and 26 healthy (control) individuals (age range, 50-85 y; mean age, 60 +/- 9 y) were examined. A 925-MBq (25 mCi) dose of (99m)Tc-TRODAT-1 was injected intravenously, and brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific striatal (99m)Tc-TRODAT-1 binding was measured and compared. RESULTS: After a region-of-interest analysis of the images from VP patients, Parkinson's disease patients, and healthy volunteers was performed to obtain ratios of putamen to occipital and striatal to occipital binding as a measurement of specific binding to the dopamine transporters in these regions of the brain, where dopamine neurons are concentrated, the specific binding in the 14 VP patients was slightly lower than but not statistically different from that of the healthy individuals in both putamen and caudate areas. A significant decrease in uptake of (99m)Tc-TRODAT-1 in the striatum (P<0.01) was found in Parkinson's disease patients. Reduction of the uptake was more pronounced in the contralateral putamen of Parkinson's disease patients than that of VP patients (P<0.001). A significant bilateral striatal asymmetry was also observed in Parkinson's disease patients but not in VP patients (P< 0.01). CONCLUSION: Our findings clearly show that, for VP patients, (99m)Tc-TRODAT-1 SPECT is a reliable method to differentiate VP from Parkinson's disease. Further studies, including those to differentiate Parkinson's disease from arteriosclerotic parkinsonism and patients with both VP and Parkinson's disease, are needed to help rule out the possibility of Parkinson's disease as early as possible.     

Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET

The goal of this study was to perform a systematic, semi-quantitative analysis of limbic perfusion in patients with Alzheimer's disease (AD) using coregistered single-photon emission tomography (SPET) images aligned to magnetic resonance (MR) images. Limbic perfusion in 40 patients with mild to moderate AD was compared with that of 17 age-, sex-, and education-matched normal controls (NC). HMPAO SPET scans and 3D T1-weighted MR images were acquired for each subject. Structures of the limbic system (i.e. hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area and cingulate, orbitofrontal and parahippocampal cortices) were traced on the MR images and transferred to the coregistered SPET scans. Perfusion ratios for all limbic regions were calculated relative to cerebellar perfusion. General linear model multivariate analysis revealed that, overall, limbic structures showed significant hypoperfusion (F=7.802, P<0.00001, eta (2)=0.695 ) in AD patients compared with NC. Greatest differences (d > or = 0.8) were found in the hippocampus, as well as all areas of the cingulate cortex. Significant relative hypoperfusion was also apparent in the parahippocampal cortex, amygdala/entorhinal cortex, septal area and anterior thalamus, all of which showed medium to large effect sizes (d=0.6-0.8). No significant relative perfusion differences were detected in the basal forebrain, hypothalamus, mamillary bodies or orbitofrontal cortex. Logistic regression indicated that posterior cingulate cortex perfusion was able to discriminate AD patients from NC with 93% accuracy (95% sensitivity, 88% specificity). The current results suggest that most, but not all, limbic structures show significant relative hypoperfusion in AD. These findings validate previous post-mortem studies and could be useful in improving diagnostic accuracy, monitoring disease progression and evaluating potential treatment strategies in AD.     

Accuracy of dipyridamole SPECT imaging in identifying individual coronary stenoses and multivessel disease in women versus men

BACKGROUND: Older women frequently undergo dipyridamole perfusion imaging and can have advanced coronary artery disease, but little data exist on the accuracy of perfusion imaging in detecting disease in individual vascular territories and multivessel disease in women, compared with men. METHODS AND RESULTS: From a database of patients undergoing myocardial single photon emission computed tomography (SPECT) perfusion imaging, 107 unselected sequential patients (58 women, 49 men) who underwent sestamibi dipyridamole stress and cardiac catheterization within 6 months of each other were identified. Data were analyzed to compare sensitivities for detection of individual coronary stenoses and multivessel disease. The concordance between perfusion image results and cardiac catheterization for individual coronary territories for women was 75%, and for men, it was 65% (P = .09). In women, the presence of disease of the left anterior descending coronary artery was detected more frequently than it was in men, 84% versus 44% (P = .004). The detection of disease in the territories of the left circumflex and right coronary arteries was similar for both groups. For women, the accuracy of perfusion imaging in identifying the presence/absence of multivessel coronary disease was 64%, compared with 71 % for men (P = not significant). CONCLUSIONS: The accuracy of dipyridamole sestamibi SPECT imaging in detecting multivessel disease was similar for men and women. The sensitivity of dipyridamole sestamibi SPECT imaging in detecting disease of the left anterior descending artery was better in women.     

201Tl and 99mTc-MIBI gated SPECT in patients with large perfusion defects and left ventricular dysfunction: comparison with equilibrium radionuclide angiography.

Left ventricular ejection fraction (LVEF) is a major prognostic factor in coronary artery disease and may be computed by 99mTc-methoxyisobutyl isonitrile (MIBI) gated SPECT. However, 201Tl remains widely used for assessing myocardial perfusion and viability. Therefore, we evaluated the feasibility and accuracy of both 99mTc-MIBI and 201Tl gated SPECT in assessing LVEF in patients with myocardial infarction, large perfusion defects and left ventricular (LV) dysfunction. METHODS: Fifty consecutive patients (43 men, 7 women; mean age 61 +/- 17 y) with a history of myocardial infarction (anterior, 26; inferior, 18; lateral, 6) were studied. All patients underwent equilibnum radionuclide angiography (ERNA) and rest myocardial gated SPECT, either 1 h after the injection of 1110 MBq 99mTc-MIBI (n = 19, group 1) or 4 h after the injection of 185-203 MBq 201Tl (n = 31, group 2) using a 90 degrees dual-head camera. After filtered backprojection (Butterworth filter: order 5, cutoff 0.25 99mTc or 0.20 201Tl), LVEF was calculated from reconstructed gated SPECT with a previously validated semiautomatic commercially available software quantitative gated SPECT (QGS). Perfusion defects were expressed as a percentage of the whole myocardium planimetered by bull's-eye polar map of composite nongated SPECT. RESULTS: Gated SPECT image quality was considered suitable for LVEF measurement in all patients. Mean perfusion defects were 36% +/- 18% (group 1), 33% +/- 17% (group 2), 34% +/- 17% (group 1 + group 2). LVEF was underestimated using gated SPECT compared with ERNA (34% +/- 12% and 39% +/- 12%, respectively; P = 0.0001). Correlations were high (group 1, r= 0.88; group 2, r = 0.76; group 1 + group 2, r = 0.82), and Bland-Altman plots showed a fair agreement between gated SPECT and ERNA. The difference between the two methods did not vary as LVEF, perfusion defect size or seventy increased or when the mitral valve plane was involved in the defect. CONCLUSION: LVEF measurement is feasible using myocardial gated SPECT with the QGS method in patients with large perfusion defects and LV dysfunction. However, both 201Tl and 99mTc-MIBI gated SPECT similarly and significantly underestimated LVEF in patients with LV dysfunction and large perfusion defects.