Usefulness of Ictal and Interictal 99mTC Ethyl Cysteinate Dimer Single Photon Emission Computed Tomography in Patients with Refractory Partial Epilepsy

Summary: Purpose: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in ～90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for ～6 h. facilitating the performance of ictal studies. Methods: In a prospective, open-label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of ^99mTc-ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal ^99mTc-ECD SPECT. Results: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases. Conclusions: ^99mTc-ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc-ECD are similar to those reported with ^99mTc-HMPA0. Because ^99mTc-ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.     

Reversible abnormal functional neuroimaging presentations in polycythemia vera with chorea

We report a case of polycythemia vera with chorea in which the brain metabolism and dopamine system were investigated using 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) and ^99mTc-labeled tropane dopamine transporter (^99mTc-TRODAT-1) single photon emission computed tomography (SPECT). Along with normalization of the hematocrit and clinical symptoms after consecutive phlebotomies, the FDG PET scan and ^99mTc-TRODAT-1 SPECT images returned towards normal. It is hypothesized that the development of polycythemia chorea is associated with a reversible alteration in the corticobasal ganglia metabolism and disturbed dopaminergic function.     

Optimized data preprocessing for multivariate analysis applied to 99mTc-ECD SPECT data sets of Alzheimer's patients and asymptomatic controls

Multivariate image analysis has shown potential for classification between Alzheimer''s disease (AD) patients and healthy controls with a high-diagnostic performance. As image analysis of positron emission tomography (PET) and single photon emission computed tomography (SPECT) data critically depends on appropriate data preprocessing, the focus of this work is to investigate the impact of data preprocessing on the outcome of the analysis, and to identify an optimal data preprocessing method. In this work, technetium-99methylcysteinatedimer (^99mTc-ECD) SPECT data sets of 28 AD patients and 28 asymptomatic controls were used for the analysis. For a series of different data preprocessing methods, which includes methods for spatial normalization, smoothing, and intensity normalization, multivariate image analysis based on principal component analysis (PCA) and Fisher discriminant analysis (FDA) was applied. Bootstrap resampling was used to investigate the robustness of the analysis and the classification accuracy, depending on the data preprocessing method. Depending on the combination of preprocessing methods, significant differences regarding the classification accuracy were observed. For ^99mTc-ECD SPECT data, the optimal data preprocessing method in terms of robustness and classification accuracy is based on affine registration, smoothing with a Gaussian of 12 mm full width half maximum, and intensity normalization based on the 25% brightest voxels within the whole-brain region.     

A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder

Data on functional imaging of bipolar disorder (BD) utilizing single photon emission computerized tomography (SPECT) is limited. This study assessed regional cerebral blood flow (rCBF), using ^99mTc-ECD SPECT, among patients with BD, with mania (N=10) or depression (N=10), compared with 10 patients with unipolar depression and 10 normal controls. Regions of interest were analysed using a semi-automatic brain quantification programme. Compared to controls, patients with mania had significantly reduced perfusion mainly in the left frontal area, also in the left anterior cingulate and parietal cortices; those with bipolar depression had significantly lowered rCBF principally in the anterior temporal regions bilaterally, as well as the left parietal area. Patients with unipolar depression had significantly lowered perfusion than controls in most of the regions examined, chiefly in the anterior temporal and frontal cortices bilaterally; they also had lowered perfusion in the right anterior temporal and frontal areas, as well as the right middle temporal area and the right thalamus, compared to patients with mania. Increased severity of psychotic symptoms was associated with reduced rCBF in patients. These results indicate that altered blood flow in the frontal-subcortical systems characterises patients with BD, as well as those with unipolar depression.     

Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS

Hypoperfusion on single-photon emission computed tomography (SPECT) of the stroke-like lesion (SLL) at the hyperacute stage of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) is considered to be a supportive evidence of the mitochondrial angiopathy theory. Our objectives were to examine whether other neuroimages, especially transcranial color-coded sonography (TCCS), done at the hyperacute stage of stroke-like episode (SLE) is consistent with hypoperfusion of the SLL. We reviewed the magnetic resonance imaging (MRI), SPECT, cerebral angiography, and TCCS of a patient with MELAS syndrome, all of which were performed at the hyperacute stage of one SLE. MRI on the 1st day post SLE showed right temporoparietal lesion with vasogenic edema. SPECT on the 2nd day showed focal decreased uptake of technetium-99m hexamethylpropyleneamine oxime (^99mTc-HMPAO) in the same region, but cerebral angiography and TCCS on the 3rd day showed increased regional cerebral blood flow (rCBF) and distal arteriole dilation in the same region. TCCS can delineate increased rCBF of the SLL at the hyperacute stage of SLE. We propose that the discrepancy between the decreased ^99mTc-HMPAO uptake and increased rCBF might be caused by mitochondrial dysfunction. The phenomenon of “hypoperfusion” on SPECT might be caused by cell dysfunction but not decreased rCBF. We suggest that SPECT can be complemented by angiography and TCCS in future studies to delineate the perfusion status of SLLs.     

Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: Assessing the efficacy of F-FDG PET,C-methionine PET and perfusion MRI

Purpose

The authors analyzed the characteristics of perfusion magnetic resonance imaging (MRI), ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ¹¹C-methionine (MET) PET to compare the efficacies of these modalities in making the distinction between radiation necrosis and tumor recurrence of high-grade glioma.

Patients and methods

Ten patients were evaluated with dynamic susceptibility contrast perfusion MRI, ¹¹C-MET PET and ¹⁸F-FDG PET to visualize gadolinium-enhanced lesions during the post-radiation follow-up period. In the perfusion MRI, four regions of interest (ROIs) were identified and average values were calculated. A reference ROI of the same size was defined in the contralateral white matter to obtain the relative cerebral blood volume (rCBV). After coregistering the PET images with the MRI, we measured the maximum uptake values of the lesion and of the contralateral cerebral white matter as reference area to calculate the L_max/R_max ratio.

Results

The rCBV was higher in the recurrence group than in the necrosis group (p = 0.010). There was no difference between groups in terms of the L_max/R_max ratio as derived from the ¹⁸F-FDG and ¹¹C-MET PET.

Conclusion

A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the L_max/R_max ratio as derived from ¹⁸F-FDG and ¹¹C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.     

Dissociation of 99mTc-ECD and 99mTc-HMPAO distributions in herpes simplex encephalitis

In herpes simplex encephalitis (HSE), the authors noted an evident dissociation between the ^99mTc-ethyl cysteinate dimer (ECD) and ^99mTc-d,l-hexamethyl-propylene- amine oxime (HMPAO) single photon emission computed tomographies (SPECTs). The patient was a 5-year-old boy with diffuse type of pontine glioma, which was treated with hyperfractionated radiotherapy. Two weeks after the completion of radiation therapy, a lesion suggesting that of HSE was noted in the right frontotemporal region on magnetic resonance images. ^99mTc-HMPAO SPECT showed an increased accumulation of the tracer in this lesion. On the ^99mTc-ECD dynamic SPECT, an exaggerated accumulation of the tracer was noted within 80 s of administration, followed by a rapid drop in the accumulation, resulting in a low accumulation in 10 min. It was assumed that this dissociation was due to the different mechanisms to trap HMPAO and ECD in the brain tissue. Received: 30 September 1995 Revised: 29 February 1996     

Brain perfusion SPECT and EEG findings in children with autism spectrum disorders and medically intractable epilepsy

Objective: We performed brain perfusion single-photon emission computed tomography (SPECT) to detect the abnormal brain region in children with both autism spectrum disorders (ASD) and medically intractable epilepsy. Methods: Fifteen children aged 4–16 years underwent multimodal examinations (MRI, interictal and/or ictal ECD-SPECT, EEG and MEG) to investigate their indications for surgical treatment. All children were diagnosed with ASD according to DSM-IV criteria and intractable epilepsy. Despite medical treatment for more than a year, all experienced at least one seizure per month. All had no underlying basic disorders. Each SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). The relationship between the eZIS pattern and EEG abnormalities or clinical symptoms was investigated. Results: All children showed focal abnormal patterns on eZIS and focal spikes on EEG. In all children, eZIS revealed a mixed hypoperfusion pattern, especially in the prefrontal cortex, medial frontal cortex, anterior cingulate cortex, medial parietal cortex, and/or anterior temporal cortex. In seven of 12 children who underwent interictal SPECT studies, areas of hypoperfusion were related to the focus observed on EEG; in six children, the focal EEG spikes represented areas of hyperperfusion. The children were divided into two groups according to the main type of hypoperfusion patterns seen on eZIS; medial-cingulate type and temporal type. No significant relationship was observed between the areas of hypoperfusion and clinical symptoms. eZIS showed the epileptic focus clearly on ictal SPECT. Conclusions: SPECT was useful to detect the abnormal brain region not only in searching for the epileptic focus but also in assessing the low or high functioning region of the brain.     

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity.

BACKGROUND: Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS: Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS: Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION: Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.     

PET imaging of ischemia-induced impairment of mitochondrial complex I function in monkey brain

To assess the capability of ¹⁸F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (¹⁸F-BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a specific marker of ischemia-induced neuronal death without being disturbed by inflammation, translational research was conducted using an animal PET in ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hours, then PET scans were conducted at Day-7 with ¹⁵O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolism of oxygen (rCMRO₂), and ¹⁸F-BCPP-EF for MC-I with arterial blood sampling. On Day-8, the additional PET scans conducted with ¹¹C-flumazenil (¹¹C-FMZ) for central-type benzodiazepine receptors, ¹¹C-PBR28 for translocator protein, and ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) for regional cerebral metabolic rate of glucose (rCMRglc). The total distribution volume (V_T) values of ¹⁸F-BCPP-EF showed the significant reduction in MC-I activity in the damaged area at Day-7. When correlated with rCBF and rCMRO₂, the V_T values of ¹⁸F-BCPP-EF provided better correlation with rCMRO₂ than with rCBF. In the inflammatory regions (region of interest, ROI_PBR) of the ischemic hemisphere detected with ¹¹C-PBR28, higher ¹⁸F-FDG uptake and lower V_T of ¹⁸F-BCPP-EF, ¹¹C-FMZ, and rCMRO₂ than those in normal contralateral hemisphere were observed. These results strongly suggested that ¹⁸F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where ¹⁸F-FDG could not owing to its high uptake into the activated microglia.     

Successful hemispherotomy in two refractory epilepsy patients with cerebral hemiatrophy and contralateral EEG abnormalities

We describe two cases of refractory epilepsy with cerebral hemiatrophy and contralateral electroencephalographic (EEG) abnormalities, in which hemispherotomy of the atrophic hemisphere effectively controlled seizures. Case 1 was a 5-year-1-month-old girl with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm. Magnetic resonance imaging showed left porencephaly corresponding to a left middle cerebral artery infarction. Case 2 was a 3-year-8-month-old boy with refractory bilateral asymmetrical tonic posturing seizures predominantly in the right arm due to atrophy of the left cerebral hemisphere after septic meningitis. Both patients had right hemiparesis and was incapable of pinching by the right hand. Contralateral interictal and ictal EEG abnormalities were observed. Interictal ^99mTc-ethyl cysteinate dimer (^99mTc-ECD) single photon emission computed tomography (SPECT) showed hypoperfusion and ictal ^99mTc-ECD-SPECT showed hyperperfusion within the left cerebral hemisphere. Left hemispherotomy was performed. Cases 1 and 2 remained seizure-free at the last follow-up 18?months and 15?months, respectively, after surgery, and contralateral interictal EEG abnormalities disappeared. In patients with cerebral hemiatrophy and contralateral EEG abnormalities, epilepsy surgery may be considered when the laterality of seizure semiology, functional imaging findings and motor deficits were concordant with the atrophic side. Ictal SPECT is effective to confirm the epileptogenic hemisphere.     

Diffuse subcortical band heterotopia,periodic limb movements during sleep and a novel “de novo” mutation in the DCX gene

Mutations of the DCX gene (Xp22.3) cause X-linked lissencephaly in males and double cortex syndrome (DCS) or subcortical band heterotopia (SBH) in females. SBH is characterized by bilateral bands of grey matter interposed in the white matter between the cortex and the lateral ventricles. The main clinical manifestation in patients with SBH is epilepsy, which may be partial or generalized and is intractable in approximately 65% of the patients. An association of periodic limb movements (PLMs) and SBH has not been documented previously. We describe a 2-year-old girl affected by SBH with epilepsy and periodic limb movements (PLMs), in whom a novel “de novo” missense substitution, Met1Val (M1V), was identified in the DCX gene. Physiopathological links between PLMs and SBH are discussed.     

Lassen's equation is a good approximation of permeability-surface model: new α values for 99mTc-HMPAO and 99mTc-ECD

Brain perfusion tracers like [^99mTc] d,l-hexamethyl-propyeneamine oxime (^99mTc-HMPAO) and [^99mTc] ethyl-cysteinate dimer (^99mTc-ECD) underestimate regional cerebral blood flow (rCBF) at high flow values. To improve linearity between tracer accumulation and rCBF, two different models have been proposed. One is Lassen''s correction algorithm for back-diffusion of tracer, and the other is based on the permeability-surface (PS) model for correction of low first-pass extraction. Although both these models have the same goal, they have completely different forms of equation. It was demonstrated that mathematical approximation of the PS model equation leads to Lassen''s equation. In this process, the relationship between PS, CBF values and Lassen''s parameter was acquired, and how to correct both the back-diffusion and low first-pass extraction was also demonstrated. A computer simulation confirmed that the two models provided similar consequences when the parameter value is chosen according to the relationship found. Lassen''s equation can be used to correct not only back-diffusion but also low first-pass extraction. To perform overall correction, the parameter value we have been using for decades may be too weak. I estimated that the parameter value for overall correction of HMPAO would be around 0.5, and that of ECD would be around 0.65.     

Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases

The eZIS allows computer-assisted statistical analysis of brain perfusion SPECT images. We evaluated the diagnostic value of brain perfusion SPECT using eZIS in patients with various neurodegenerative diseases at a very early stage, within one year from onset.

Methods

SPECT using eZIS was performed for patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD,), idiopathic Parkinson disease (PD) and vascular Parkinsonism (VP), multiple systemic atrophy of the cerebellar type (MSA-C), cortical cerebellar atrophy (CCA) and amyotrophic lateral sclerosis (ALS).

Results

Decreased rCBF was observed in the posterior cingulate cortex, precuneus and parietal cortex in AD; in the frontal gyrus and insula in FTD; in the occipital lobe, precuneus gyrus and posterior cingulate cortex in DLB; in the striatum and the thalamus in VP; in the cerebellum in CCA; in the cerebellum and pons in MSA-C and in the frontal cortex including the central sulcus in ALS. Increased rCBF in the striatum, thalamus and cerebellar dentate nuclei were observed in PD.

Conclusions

A specific rCBF pattern was observed for each disease using eZIS analysis, consistent with previous reports. Our results showed eZIS can be easily used as an adjunct to early-diagnosis of neurodegenerative diseases in any hospital.     

Comparison of [99mTc]HMPAO SPECT with [18F]fluoromethane PET in cerebrovascular disease

Positron emission tomography (PET) of [18F]fluoromethane (FM) and single-photon emission tomography (SPECT) of [99mTc]hexamethylpropyleneamine oxime (HMPAO) were performed under identical conditions within 2 h in 22 patients suffering from cerebrovascular disease (8 ischemic infarction, 2 intracerebral hemorrhages, 7 transient ischemic attacks, and 5 multi-infarct syndrome). While gross pathological changes could be seen in the images of either procedure, focal abnormalities corresponding to transient ischemic deficits or to lesions in multi-infarct syndrome and areas of functional deactivation were sometimes missed on SPECT images. Overall, HMPAO SPECT images showed less contrast between high and low activity regions than the FM PET images, and differences between lesions and contralateral regions were less pronounced (6.4 vs 13.3% difference). Regional cerebral blood flow (rCBF) was calculated from FM PET studies in 14 large territorial regions and the pathological lesion, and the regional values relative to mean flow were compared to the relative HMPAO uptake in an identical set of regions defined on the SPECT images. Among individual patients, the Spearman rank-correlation coefficient between relative rCBF and HMPAO uptake varied between 0.48 and 0.89, with a mean of 0.70. While an underestimation of high flow with SPECT--which was demonstrated in a curvilinear relationship between all relative regional PET and SPECT values--could be corrected by linearization taking into account HMPAO efflux from the brain before metabolic trapping, correspondence of SPECT data with PET rCBF values was not improved since this procedure also increased the variance in high flow areas. In the cerebellum, however, a high HMPAO uptake in SPECT always overestimated CBF in relation to forebrain values; this finding might be due to high capillary density in the cerebellum. The differences observed between SPECT and PET data may be explained by technical and physical properties of the methods and by the incomplete first-pass extraction of HMPAO. Additionally, HMPAO or its metabolites may leak through a damaged blood-brain barrier (as observed in one infarct and in the surrounding of hemorrhages), impairing the contrast between lesion and normal tissue. The presented data indicate that the quantification of rCBF by HMPAO SPECT is limited.     

Cerebral blood flow abnormalities in patients with neurally mediated syncope

The aim of this study is to investigate regional cerebral blood flow (rCBF) in patients with syncope. We compared brain single photon emission computed tomography (SPECT) images of neurally mediated syncope patients with those of age/sex matched healthy volunteers. ^99mTc-ethylcysteinate dimer (ECD) brain SPECT was performed in 35 patients (M/F = 17/18, mean 36.6 years) with syncope during the asymptomatic period, and in 35 healthy volunteers. For statistical parametric mapping (SPM) analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 14-mm full width at half maximum Gaussian kernel. The mean duration of syncope history was 4.9 years and the mean number of syncope episodes was 6.3. In all patients, syncope or presyncope episodes occurred during head-up tilt tests, and all were the vasodepressive type. SPM analysis of brain SPECT images showed significantly decreased rCBF in the right anterior insular cortex, left parahippocampal gyrus, bilateral fusiform gyri, bilateral middle and inferior temporal gyri, left lingual gyrus, bilateral precuneus and bilateral posterior lobes of the cerebellum in syncope patients at a false discovery rate corrected p < 0.05. There were no brain regions that showed increased rCBF in syncope patients. Furthermore, we found a negative correlation between the total number of syncopal episodes and the rCBF of the right prefrontal cortex, and between the duration of syncope history and the rCBF of the right cingulate gyrus at uncorrected p < 0.001. Decreases of rCBF in multiple brain regions may be responsible for autonomic dysregulation and improper processing of emotional stress in neurally mediated syncope patients, and frequent syncope episodes may lead to frontal dysfuction.     

Cerebral blood flow abnormality in patients with idiopathic generalized epilepsy

Purpose

To investigate the regional cerebral blood flow (rCBF) changes in patients with idiopathic generalized epilepsy (IGE), we compared brain single photon emission computed tomography (SPECT) images of drug naïve IGE patients with those of age/sex matched healthy volunteers.

Methods

Brain interictal ^99mTc-ethylcysteinate dimer SPECT was performed in 21 patients with IGE (M/F = 10/11, 21.3 ± 2.7 years) and 21 normal controls. The seizure types were generalized tonic-clonic seizure in 14 patients and myoclonic seizures with rare generalized tonic-clonic seizures in seven. Differences of rCBF between an IGE group and a normal control group were examined by the statistical parametric mapping (SPM) of brain SPECT images using independent t test.

Results

The SPM analysis showed that the rCBF of the IGE patients was significantly reduced in the anterior and posterior cingulate gyri, bilateral anterior nuclei and right dorsolateral nucleus of the thalamus, right superior colliculus of the midbrain, and the cerebellum at the level of uncorrected p < 0.005. In the small volume correction analysis for the thalamus and brainstem, the rCBF was also significantly decreased in the same brain regions at the level of FDR corrected p < 0.05. No brain regions of the IGE patients had increased rCBF.

Conclusion

Our study demonstrates that the interictal rCBF in drug naive IGE patients is reduced in the cingulate gyrus, thalamus, brainstem and cerebellum. This result suggests that dysfunctions in these brain regions are associated with IGE.

     

Longitudinal Imaging of Regional Brain Volumes,SV2A,and Glucose Metabolism In Huntington's Disease

Background

Development of disease-modifying treatments for Huntington's disease (HD) could be aided by the use of imaging biomarkers of disease progression. Positron emission tomography (PET) with ¹¹C-UCB-J, a radioligand for the brain-wide presynaptic marker synaptic vesicle protein 2A (SV2A), detects more widespread brain changes in early HD than volumetric magnetic resonance imaging (MRI) and ¹⁸F-fludeoxyglucose (¹⁸F-FDG) PET, but longitudinal ¹¹C-UCB-J PET data have not been reported. The aim of this study was to compare the sensitivity of ¹¹C-UCB-J PET, ¹⁸F-FDG PET, and volumetric MRI for detection of longitudinal changes in early HD.

Methods

Seventeen HD mutation carriers (six premanifest and 11 early manifest) and 13 healthy controls underwent ¹¹C-UCB-J PET, ¹⁸F-FDG PET, and volumetric MRI at baseline (BL) and after 21.4 ± 2.7 months (Y2). Within-group and between-group longitudinal clinical and imaging changes were assessed.

Results

The HD group showed significant 2-year worsening of Unified Huntington's Disease Rating Scale motor scores. There was significant longitudinal volume loss within the HD group in caudate (−4.5% ± 3.8%), putamen (−3.6% ± 3.5%), pallidum (−3.0% ± 2.7%), and frontal cortex (−2.0% ± 2.1%) (all P < 0.001). Within the HD group there was longitudinal loss of putaminal SV2A binding (6.4% ± 8.8%, P = 0.01) and putaminal glucose metabolism (−2.8% ± 4.4%, P = 0.008), but these changes were not significant after correction for multiple comparisons. Premanifest subjects at BL only had significantly lower SV2A binding than controls in basal ganglia structures, but at Y2 additionally had significant SV2A loss in frontal and parietal cortex, indicating spread of SV2A loss from subcortical to cortical regions.

Conclusions

Volumetric MRI may be more sensitive than ¹¹C-UCB-J PET and ¹⁸F-FDG PET for detection of 2-year brain changes in early HD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBF. Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient ^99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15 % was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17 %) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration. Received: 3 November 2000 / Received in revised form: 12 January 2001 / Accepted: 24 January 2001