Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer's disease: additional results from the AMBAR study.

PURPOSE: This study was designed to detect structural and functional brain changes in Alzheimer's disease (AD) patients treated with therapeutic plasma exchange (PE) with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial. METHODS: Mild-to-moderate AD patients were randomized into four arms: three arms receiving PE with albumin (one with low-dose albumin, and two with low/high doses of albumin alternated with IVIG), and a placebo (sham PE) arm. All arms underwent 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Magnetic resonance imaging (MRI) volumetric analyses and regional and statistical parametric mapping (SPM) analysis on 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) were performed. RESULTS: MRI analyses (n = 198 patients) of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group (p < 0.05 in 3 structures vs. 4 to 9 in other groups). The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. SPM 18FDG-PET analyses (n = 213 patients) showed a worsening of metabolic activity in the specific areas affected in AD (posterior cingulate, precuneus, and parieto-temporal regions). The high-albumin + IVIG treatment group showed the greatest metabolic stability over the course of the study, i.e., the smallest percent decline in metabolism (MaskAD), and least progression of defect compared to placebo. CONCLUSIONS: PE with albumin replacement was associated with fewer deleterious changes in subcortical structures and less metabolic decline compared to the typical of the progression of AD. This effect was more marked in the group treated with high albumin + IVIG. TRIAL REGISTRATION: (AMBAR trial registration: EudraCT#: 2011-001,598-25; ClinicalTrials.gov ID: NCT01561053).

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study.

BACKGROUND: To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC). METHODS: This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient's age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis. RESULTS: Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant). CONCLUSIONS: CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.

Warranty periods for normal myocardial perfusion stress SPECT.

BACKGROUND: To assess different warranty periods following a normal myocardial perfusion SPECT based on patients' clinical characteristics and the type of stress performed. METHODS AND RESULTS: A study was done of 2,922 consecutive patients (62.9 ± 13 years; 53.4% women) with a normal stress-rest SPECT. The warranty period was defined as the period during which patients remained at a low risk (<1% events/year) of total mortality (TM), or hard events (HE) (cardiac death or non-fatal myocardial infarction). Of these patients, 2,051 were given an exercise myocardial perfusion imaging (Ex-MPI); 461 submaximal exercise plus dipyridamole (Ex+Dipy-MPI); and 410 dipyridamole (Dipy-MPI). During a mean follow-up of 5 ± 3.3 years, a significant reduction (P < .05) of the warranty period for TM (13.5, 9.6 and 8 months) and HE (34.8, 20.5 and 8.2 months) was observed, for Ex-MPI, Ex+Dipy-MPI and Dipy-MPI, respectively. Other warranty period determinants were the clinical variables of age, sex, diabetes and known coronary artery disease. An abnormal left ventricular ejection fraction on gated-SPECT also significantly shortened the warranty period for HE in patients undergoing Ex+Dipy-MPI (P = .001) or Dipy-MPI alone (P = .007). CONCLUSIONS: The warranty period for a normal stress-rest SPECT is highly variable since it is primarily determined by the type of stress, the patient's clinical characteristics and LVEF.

Long-term follow-up assessment after the arterial switch operation for correction of dextro-transposition of the great arteries by means of exercise myocardial perfusion-gated SPECT.

The arterial switch operation (ASO) is the preferred technique for correcting transposition of the great arteries, but translocation and reimplantation of the coronary arteries can produce myocardial ischemia. This report aims to describe the authors' experience with exercise single-photon emission computed tomography (SPECT) used to evaluate myocardial perfusion. Exercise-rest gated-myocardial perfusion SPECT was performed for 69 patients (49 boys; median age, 9 years; 5th percentile [6.4 years] to 95th percentile [15.6 years]), 64 of whom were asymptomatic 9.98 ± 3.20 years after ASO. During exercise testing, the patients reached 9.85 ± 3.05 metabolic equivalents (METs) and a median heart rate of 160 beats per minute (bpm), 5th percentile (106 bpm) to 95th percentile (196 bpm). Whereas 61 patients (88.41 %) had normal myocardial perfusion, 2 patients (2.9 %) had reversible defects, and 6 patients (8.7 %) had fixed defects. All the patients with perioperative ischemic complications (4/4, 100 %) had myocardial perfusion defects, whereas four patients (4/65, 6.15 %) without ischemic complications had abnormal perfusion (p = 0.0005). Age at the time of surgery did not differ significantly (p = 0.234) between the patients with perfusion defects and those with normal study results. No significant difference was observed between the patients who had an A coronary pattern (left coronary artery originating from the left sinus and the right coronary artery originating from the right sinus, n = 47) and those who had a non-A coronary pattern (n = 22) (p = 1). The high rate for normality of exercise myocardial perfusion in our study suggests that myocardial perfusion gated-SPECT should be reserved for patients who have experienced perioperative ischemic complications or those with symptoms, at least during the first 10 years after the surgery.

Predictive variables for hard cardiac events and coronary revascularization in patients with normal left ventricular myocardial perfusion and systolic function.

BACKGROUND: The objective of this study was to investigate the impact of clinical, electrocardiographic and stress testing variables in predicting hard cardiac events (HE) and coronary revascularization (CR) in patients with normal stress-rest gated SPECT. MATERIALS AND METHODS: Included in the study were 2,004 patients (63.5 ± 12.5 years, 41.6% men) with normal myocardial perfusion and left ventricular ejection fraction (LVEF) >50% on gated SPECT who were followed for HE (cardiovascular death or acute myocardial infarction) and CR. RESULTS: During a follow-up of 4.3 ± 2.4 years, 33 patients (1.6 %; 0.4%/year) had HE and 50 patients (2.5%; 0.6%/year) underwent CR. In a univariate analysis, age ≥65 years, insulin-dependent diabetes mellitus (IDDM), left bundle branch block (LBBB), and pharmacological stress were associated with HE. Independent predictors of HE were age ≥65 years (p < 0.001; HR 6.9), IDDM (p = 0.014; HR 3.4), and LBBB (p = 0.002; HR 4.6). In the univariate analysis, male gender, LVEF, known coronary artery disease (CAD), LBBB, and a positive stress test were associated with CR. Independent predictors of CR were known CAD (p = 0.016; HR 2.1), and a positive stress test (p = 0.006; HR 2.3). CONCLUSION: Age ≥65 years, IDDM, and LBBB are HE-independent predictors in patients with normal myocardial perfusion and normal LVEF on gated SPECT. The presence of known CAD or a positive stress test significantly increases the probability of CR during follow-up.

Paradoxical scintigraphic pattern in regions with myocardial necrosis on myocardial perfusion gated SPECT with 99mTc-tetrofosmin.

OBJECTIVES: To assess the significance of a paradoxical pattern (PP) (greater tracer uptake during stress than at rest) on gated myocardial perfusion SPECT in myocardial regions with myocardial necrosis. METHODS: A review of 1,764 consecutive stress-rest myocardial perfusion SPECT studies in patients with prior myocardial infarction (MI) was conducted. Of these, 117 patients (6.6%) with a PP corresponding to a region with myocardial necrosis were identified. An assessment of perfusion, contractility, wall thickening, scintigraphic criteria for viability, and the characteristics of the culprit artery in regions with a PP was performed. RESULTS: Of the 160 regions with necrosis, 125 (75%) had a PP: 67 in the anterior region and 58 in the inferior-lateral region. In the PP group, the average tracer activity of defects during stress was significantly higher than at rest (P < .0001). Ninety-three (86.6%) out of 110 PP segments without scintigraphic criteria of viability at rest met viability criteria on stress imaging. The artery supplying regions with a PP was patent in 88% of cases. In the remaining patients it was occluded, although collateral circulation was always present. CONCLUSIONS: In scintigraphic segments corresponding to regions with infarction and PP, a mixture of viable and well perfused myocardium was observed. In most cases, the vessel that supplied the region with PP was either patent, or when the artery was occluded, there was evident collateral circulation.

Interassay reproducibility of myocardial perfusion gated SPECT in patients with atrial fibrillation.

AIM: The aim of this study was to assess interassay reproducibility of myocardial perfusion gated-SPECT for calculation of end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) in patients with atrial fibrillation (AF). METHODS: One hundred and fifteen consecutive patients with AF from three participating hospitals (mean age 68.9 years, 39 women) were included in the study. All patients underwent two image gated acquisitions at rest with a 30 minute interval between them. Quantitative data were obtained using the QGS and ECT software algorithms. RESULTS: Heart rate was similar in both studies: 74.94 +/- 15.2 vs 73.03 +/- 15.57. QGS yielded an LVEF of 54.4%/53.8%, an EDV of 100 mL/101.5 mL, and an ESV of 51 mL/52.3 mL; and ECT showed an LVEF of 63.6%/62.9%, an EDV of 125.8 mL/127.4 mL and ESV of 54.1 mL/56.3 mL. Correlation between the two acquisitions was high (>0.948) for both methods for LVEF, EDV and ESV. Regression and Bland-Altman graphics showed a good agreement between all parameters. Interassay variation coefficients for each method (QGS/ECT) were 5.29% vs 4.83% for LVEF, 4.94% vs 5.17% for EDV, and 9.94% vs 12.78% for ESV. CONCLUSIONS: Interassay reproducibility of LVEF and EDV with gated-SPECT in patients with AF is good, whereas for ESV it is suboptimal, particularly when ESV is small.

Long-term follow-up of differentiated thyroid carcinoma in children and adolescents.

Objectives The aims were to analyze the clinical features, response to treatment, prognostic factors and long-term follow-up of children and adolescents with differentiated thyroid carcinoma (DTC). Methods Eighty patients with DTC were studied retrospectively. All underwent total or near-total thyroidectomy, and in 75 cases, ablative iodine therapy was recommended. Patients were assessed periodically by tests for serum thyroglobulin levels and whole-body iodine scans. Age, gender, initial clinical presentation, histology, tumor stage, postoperative complications, radioiodine treatment protocol, treatment response, thyroglobulin (Tg), recurrence and long-term disease progression were evaluated. Results Seventy patients completed >2 years of follow-up (23 males, 47 females; median age: 14 years; range: 3-18 years). Sixty-two patients showed papillary DTC and eight, follicular DTC. Sixty-five percent presented nodal metastasis and 16%, pulmonary metastasis at diagnosis. Six months after first radioiodine treatment, 36.2% of patients were free of disease. Seven recurrences were documented. At the end of follow-up, overall survival was 100%, and 87.2% of patients were in complete remission. Nine patients had persistent disease. We found a significant association between stage 4 and persistent disease. Hundred percent of patients with negative Tg values at 6 months posttreatment were documented free of disease at the end of the follow-up. The analysis of disease-free survival based on radioiodine treatment protocols used showed no statistically significant differences. Conclusions DTC in children and adolescents is frequently associated with presence of advanced disease at diagnosis. Despite this, complete remission was documented after treatment in most cases, with a good prognosis in the long-term follow-up. Negative posttreatment thyroglobulin and stage 4 at diagnosis were significant prognostic variables.

Utility of the 18F-Florbetapir positron emission tomography in systemic amyloidosis.

Amyloidosis comprises a group of heterogeneous conditions. To ascertain the burden of disease is important because it can determine the treatment as well as the evolution of the disease. Recent reports have shown good results in diagnosing cardiac amyloidosis using 18F-florbetapir. We hypothesize that combining whole body PET/CT with 18F-Florbetapir can be useful to characterize the burden of the disease. We included 25 patients, 13 of them with different types of amyloidosis, and 12 with Alzheimer's disease as controls. Target-to-background ratio was computed for multiple organ using maximum standardized uptake values. Organ involvement was described (standardized techniques versus PET) according to different kinds of amyloidosis showing promising results in AA and AL types. Heart involvement showed poorer results when compared to tongue, lung or thyroid gland. Multiple organ involvement in patients previously labelled as having negative organ affectation could be identified. This is the first study to evaluate the utility of 18F-florbetapir in the assessment of the global extension of disease. Our results show that this technique is useful for its diagnosis.

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer's Disease Patients Treated with Plasma Exchange with 5% Human Albumin.

BACKGROUND: Recently, modifications of Aß1-42 levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. OBJECTIVE: To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. METHODS: Patients received between 3 and 18 PE with albumin (Albutein® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. RESULTS: 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. CONCLUSIONS: Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion.

Gated-SPECT equilibrium radionuclide angiography in right ventricular assessment of patients with repaired tetralogy of Fallot.

BACKGROUND: The long-term prognosis of patients with tetralogy of Fallot (TF) who have undergone repair is determined by right ventricular dilatation resulting from residual pulmonary insufficiency. We have studied the values of right and left ventricle systolic function obtained by gated single photon emission computed tomography (SPECT) equilibrium radionuclide angiography (ERNA) in these patients. METHODS: A study population of 62 patients with surgically repaired TF underwent gated-SPECT ERNA to determine ejection fraction of the right and left ventricle and dimensions of the right ventricle and pulmonary infundibulum. Results were compared with those of a group of 11 patients without heart disease. RESULTS: RVEF (34% vs. 40%, P=0.02) and LVEF (49% vs. 54%, P=0.03) were significantly lower in patients with TF than in the control group. The RVEF and LVEF variation coefficients were 9% and 6.2%, respectively. Volumes of the right ventricle (P=0.003) were significantly greater than those of the control group, although variation coefficients were 15%. CONCLUSIONS: Gated-SPECT ERNA is a non-invasive method of assessing ejection fraction in patients with repaired TF. In these patients, the ejection fraction is decreased in both ventricles, whereas size of the right ventricle is significantly increased. Reproducibility of the RVEF calculation is good, but in the case of volumes it is suboptimal.

Role of [(11)C] methionine positron emission tomography in the diagnosis and prediction of survival in brain tumours.

OBJECTIVE: [(11)C] methionine (MET) positron-emission tomography (PET) is a useful diagnostic and therapeutic tool in neuro-oncology. The aim of this study was to evaluate the relationship between MET uptake and the histopathological grade in both primary brain tumours and brain metastases. A secondary goal was to assess the relationship between MET uptake and patients' survival after surgery. METHODS: We reviewed a consecutive series of 43 PET studies performed at our institution. Out of the 43 patients studied, 35 harboured primary brain tumours (3 grade I, 12 grade II, 7 grade III and 13 grade IV) and 8 patients had brain metastases. We measured the tumour/cortex ratio (T/C ratio) on each PET study and we investigated the correlations among the tracer uptake, tumour grade, tumour type, MRI parameters and outcome. RESULTS: The mean T/C ratio was 1.8 ± 0.9 for benign lesions and low grade gliomas (grade I and II) and 2.7 ± 1 for high grade gliomas (grade III and IV). In brain metastases it was 2.5 ± 0.7, with a significant difference in MET uptake between low and high grades gliomas (P=0.03). There was no statistically significant difference among all different histologic types. We found that both contrast enhancement and perfusion studies correlate with MET uptake in brain tumours. Moreover, in Kaplan-Meier curves, the T/C ratio adversely affects long term survival in patients with brain tumours (P=0.01). CONCLUSIONS: MET PET appears to be useful in diagnosis and evaluation of potential malignancy in brain tumours. MET uptake is also related with the overall survival in patients with brain tumours. Nevertheless, further studies are needed in order to define its possible clinical implications in identifying patients at high risk of tumour progression or resistance to therapy.

Progressive presynaptic dopaminergic deterioration in Huntington disease: a [123I]-FP-CIT SPECT two-year follow-up study.

To illustrate the potential of [I]-FP-CIT SPECT DaTSCAN® in investigating the progression of presynaptic dopaminergic degeneration in Huntington disease (HD), we performed a 2-year follow-up [I]-FP-CIT study on 4 HD patients, evaluating the SPECT imaging based on qualitative and semiquantitative analysis. The mean annual decline in [I]-FP-CIT uptake in caudate and putamen after 2 years of follow-up was 5.8% and 9.6%, respectively. Our findings suggest that [I]-FP-CIT SPECT is useful in investigating the progression of presynaptic dopaminergic degeneration in HD, and may be useful as a disease biomarker, providing an objective method for measuring the effectiveness of future neuroprotective therapies.

Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.

BACKGROUND: There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI). OBJECTIVES: To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI. METHODS: From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation. RESULTS: The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia. CONCLUSION: Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.

Gated-SPECT myocardial perfusion imaging as a complementary technique to magnetic resonance imaging in chronic myocardial infarction patients.

INTRODUCTION AND OBJECTIVES: The aim of this study was to compare magnetic resonance and gated-SPECT myocardial perfusion imaging in patients with chronic myocardial infarction. METHODS: Magnetic resonance imaging and gated-SPECT were performed in 104 patients (mean age, 61 [12] years; 87.5% male) with a previous infarction. Left ventricular volumes and ejection fraction and classic late gadolinium enhancement viability criteria (<75% transmurality) were correlated with those of gated-SPECT (uptake >50%) in the 17 segments of the left ventricle. Motion, thickening, and ischemia on SPECT were analyzed in segments showing nonviable tissue or equivocal enhancement features (50%-75% transmurality). RESULTS: A good correlation was observed between the 2 techniques for volumes, ejection fraction (P<.05), and estimated necrotic mass (P<.01). In total, 82 of 264 segments (31%) with >75% enhancement had >50% single SPECT uptake. Of the 106 equivocal segments on magnetic resonance imaging, 68 (64%) had >50% uptake, 41 (38.7%) had normal motion, 46 (43.4%) had normal thickening, and 17 (16%) had ischemic criteria on SPECT. CONCLUSIONS: A third of nonviable segments on magnetic resonance imaging showed >50% uptake on SPECT. Gated-SPECT can be useful in the analysis of motion, thickening, and ischemic criteria in segments with questionable viability on magnetic resonance imaging.

Usefulness of exercise test and myocardial perfusion-gated single photon emission computed tomography to improve the prediction of major events.

BACKGROUND: The incremental prognostic value of myocardial perfusion-gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated. METHODS AND RESULTS: Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79-0.89; P<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; P=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033). CONCLUSIONS: Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.

A two-year follow-up of cognitive deficits and brain perfusion in mild cognitive impairment and mild Alzheimer's disease.

The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.

SPECT imaging for brain improvement quantification in a patient with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene (CYP27), which leads to reduced synthesis of bile acids, particularly chenodeoxycholic acid (Cali et al, J Biol Chem. 1991;266:7779-7783; Gallus et al, Neurol Sci. 2006;27:143-149). The disease is characterized by progressive neurologic dysfunction due to accumulation of cholestanol in neurologic tissues (Moghadasian et al, Arch Neurol. 2002;59:527-529; Selva-O'Callaghan et al, Rheumatology. 2007;46:1212-1213). Long-term treatment with chenodeoxycholic acid can arrest or even reverse progression of the disease (Pierre et al, J Inherit Metab Dis. In press).Brain SPECT with 740 MBq of Tc-99m ethyl cysteinate dimmer, using a double-head gamma camera (Siemens E.cam) with high-resolution, low-energy parallel collimators was performed in our patient at onset and 2 years after starting chenodeoxycholic acid treatment. SPECT acquisitions were performed using a 360-degree orbit, 1 image/30 seg/3 degree, and 128 × 128 matrix. Reconstruction was by means of filtered back-projection, Butterworth 5/0.25, without attenuation correction. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam (Segami Corporation). To visually identify abnormal perfusion regions, volume render brain image was computed, where abnormal perfusion regions were found by comparing with age-matched normal database, and Brodmann areas (BA) were quantified. Pre- versus post-treatment changes were computed by means of relative percentage between counts. Post-treatment SPECT showed better perfusion than pretreatment SPECT with an increase between 5% and 10% in frontal cortex (BA 9, BA 24, BA 32, BA 46, BA 47), parietal cortex (BA 5, BA 31), and temporal cortex (BA 20, BA 22, BA 28, BA 36, BA 37, BA 38), and with an increase of more than 10% in frontal cortex (BA 45) and parietal cortex (BA 23). This case illustrates the benefit of bile acid therapy for halting and even reversing neurologic retardation in this condition.

Quantitative evaluation of striatal I-123-FP-CIT uptake in essential tremor and parkinsonism.

AIM: The aim of this study was to quantitatively evaluate the striatal uptake in 3 groups of patients: essential tremor (ET), drug-induced parkinsonism (DIP), and Parkinson disease (PD), using a voxel-based methodology and volumes of interests (VOIs) analysis. PATIENTS AND METHOD: Sixty patients from the Neurology Department Movement Disorders outpatient clinic in a tertiary hospital with I-123-FP-CIT SPECT were selected. After a clinical follow-up period of 2 years, a final clinical diagnosis of DIP was established for 20 patients (first group); 20 patients were diagnosed with ET (second group), and the third group was made up of 20 patients with a qualitatively pathologic SPECT who were diagnosed with PD.Once processed, DIP studies were spatially normalized to Montreal Neurologic Institute space and an average image was computed to create an I-123-FP-CIT SPECT template using statistical parametric mapping (SPM). Then all the I-123-FP-CIT images from all groups (DIP, ET, and PD) were registered to the new template. VOIs were defined in a digital atlas in Montreal Neurologic Institute space (caudate nucleus, putamen, and occipital cortex). Finally, mean counts were extracted from all VOIs and putamen-occipital and caudate-occipital ratios were computed. Analysis of variance tests were performed with all ratios.A SPM study of patterns evaluated the efficacy of the automated technique to determine whether the significant differences among groups corresponded to the same regions that the method purported to evaluate. RESULTS: The analysis of variance test revealed significant differences between DIP and ET as compared with PD, both in the putamen and in the caudate nucleus. There were significant differences between DIP and ET populations only in the putamen but not in the caudate.The SPM found a lower uptake in the PD group in comparison with the ET and DIP groups. Therefore, in the organic parkinsonism cases, the most significant changes in uptake decrease were found in the putamen nuclei when compared with the DIP and the ET cases. No significant changes were observed between the ET and DIP groups. CONCLUSIONS: This study provides a fairly simple, reproducible, and useful methodology to be applied in everyday practice to quantify the studies of dopamine transporters using FP-CIT.We present the different ratios for putamen and caudate nucleus for 3 different groups with FP-CIT images. We obtained an optimal discrimination threshold value between the reference population and the pathologic population for the putamen ratio.