Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study.

BACKGROUND AND PURPOSE: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. MATERIALS AND METHODS: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. RESULTS: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. CONCLUSIONS: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.

Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging.

The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.

X-ray computed tomography: semiautomated volumetric analysis of late-stage lung tumors as a basis for response assessments.

Background. This study presents a semiautomated approach for volumetric analysis of lung tumors and evaluates the feasibility of using volumes as an alternative to line lengths as a basis for response evaluation criteria in solid tumors (RECIST). The overall goal for the implementation was to accurately, precisely, and efficiently enable the analyses of lesions in the lung under the guidance of an operator. Methods. An anthropomorphic phantom with embedded model masses and 71 time points in 10 clinical cases with advanced lung cancer was analyzed using a semi-automated workflow. The implementation was done using the Cognition Network Technology. Results. Analysis of the phantom showed an average accuracy of 97%. The analyses of the clinical cases showed both intra- and interreader variabilities of approximately 5% on average with an upper 95% confidence interval of 14% and 19%, respectively. Compared to line lengths, the use of volumes clearly shows enhanced sensitivity with respect to determining response to therapy. Conclusions. It is feasible to perform volumetric analysis efficiently with high accuracy and low variability, even in patients with late-stage cancer who have complex lesions.

Data sets for the qualification of volumetric CT as a quantitative imaging biomarker in lung cancer.

The drug development industry is faced with increasing costs and decreasing success rates. New ways to understand biology as well as the increasing interest in personalized treatments for smaller patient segments requires new capabilities for the rapid assessment of treatment responses. Deployment of qualified imaging biomarkers lags apparent technology capabilities. The lack of consensus methods and qualification evidence needed for large-scale multi-center trials, as well as the standardization that allows them, are widely acknowledged to be the limiting factors. The current fragmentation in imaging vendor offerings, coupled with the independent activities of individual biopharmaceutical companies and their contract research organizations (CROs), may stand in the way of the greater opportunity were these efforts to be drawn together. A preliminary report, "Volumetric CT: a potential biomarker of response," of the Quantitative Imaging Biomarkers Alliance (QIBA) activity was presented at the Medical Imaging Continuum: Path Forward for Advancing the Uses of Medical Imaging in the Development of New Biopharmaceutical Products meeting of the Extended Pharmaceutical Research and Manufacturers of America (PhRMA) Imaging Group sponsored by the Drug Information Agency (DIA) in October 2008. The clinical context in Lung Cancer and a methodology for approaching the qualification of volumetric CT as a biomarker has since been reported [Acad. Radiol. 17, 100-106, 107-115 (2010)]. This report reviews the effort to collect and utilize publicly available data sets to provide a transparent environment in which to pursue the qualification activities in such a way as to allow independent peer review and verification of results. This article focuses specifically on our role as stewards of image sets for developing new tools.

Change in lung tumor volume as a biomarker of treatment response: a critical review of the evidence.

SPECIFIC AIM: To review the evidence indicating that volumetric image analysis of computed tomography scans meets specifications for qualification as a biomarker in clinical trials or the management of individual patients with lung cancer. METHODS: Claims of value were broken down into questions about technical feasibility, accuracy, the precision of measurement, sensitivity, the correlations with health outcomes, and the risks of producing misleading information. For each claim, the pertinent literature was reviewed. RESULTS: Technical feasibility has now been shown, but only in limited contexts. Accuracy has been demonstrated, but only for tumors with favorable anatomical features. Measurement error still makes the assessment of change in small nodules precarious in diagnostic settings unless rigorous image acquisition and analysis procedures are followed. Precision is sufficient in some larger masses to make volumetrics a sensitive biomarker. In a few trials, correlations with clinical outcomes have been higher for volumetric-based measures than for unidimensional or bidimensional diameters. Value in clinical practice settings and clinical trials has been suggested, but not proven. CONCLUSION: The weight of the evidence indicates there are circumstances in which volumetric image analysis adds value to clinical trial science and the practice of medicine.

[99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease.

BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's disease.

We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p < 0.0001) of PD patients compared to controls. Using the posterior putamen as the main region of interest resulted in the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.

Striatal dopamine transporters and cognitive functioning in healthy men and women.

OBJECTIVE: There is growing interest in distinguishing the biological bases of sex differences in behavior from environmental influences. Sex hormone levels seem to be related to some cognitive abilities, particularly memory, and the dopaminergic system participates in the mediation of memory. The dopamine transporter is the primary indicator of dopaminergic tone. This study investigated the relationship between cognition and dopamine transporter availability in healthy men and women. METHOD: Dopamine transporter levels were measured with a technetium-99m radiolabeled analog of cocaine, TRODAT-1, in 66 healthy volunteers (30 men and 36 women). A neuropsychological battery designed to target functions associated with dopaminergic activity was administered during the uptake interval between the radiopharmaceutical injection and image acquisition. RESULTS: Women and younger participants had higher dopamine availability in the caudate nucleus, and these groups also performed better on verbal learning tasks. Furthermore, dopamine transporter availability was correlated with learning performance within groups. Relationships between dopamine availability in the caudate and putamen and executive and motor functioning were observed in women, but not in men. CONCLUSIONS: The results provide further evidence for age effects and sex differences in the neuromodulatory influences of dopamine on behavior in humans.

Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes.

UNLABELLED: The aim of this study was to investigate the difference in the rates of FDG uptake between malignant and inflammatory cells and processes. IN VITRO STUDIES: (18)F-FDG uptake by different tumor cell lines (human mesothelioma [REN]; rat mesothelioma [II45]; mice melanoma [B18F10]; mice mesothelioma [AB12]; human myeloma [GM1500]; and human ovarian cancer [SKOV3]) and peripheral blood mononuclear cells isolated from 8 healthy human volunteers was measured 20 and 60 min after FDG was added into growth medium. Animal studies: II45 cells were implanted into the left flank of rats (n = 5) and a focal inflammatory reaction (mechanical irritation) was generated in the right flank. PET images at 45 and 90 min after injection of FDG were obtained and standardized uptake values (SUVs) were determined. Patient studies: Seventy-six patients who had dual time FDG PET scans were retrospectively analyzed. All results were expressed as the percentage change in SUV of the later time image from that of the earlier time (mean +/- SD). IN VITRO STUDIES: Except for the SKOV3 cell line, which had only minimally increased FDG uptake (+10% +/- 26%; P > 0.3), all other tumor cell lines tested showed significantly increased FDG uptake over time (GM1500, +59% +/- 19%; B18F10, +81% +/- 15%; AB12, 93% +/- 21%; II45, +161% +/- 21%; REN, +198% +/- 48%; P < 0.01 for all). By contrast, FDG uptake in mononuclear cells was decreased in 7 of 8 donors. Animal studies: SUVs of tumors from 90-min images were significantly higher than those from 45-min images (+18% +/- 8%; P < 0.01), whereas the SUVs of inflammatory lesions decreased over time (-17% +/- 13% of the early images; P < 0.05). CLINICAL STUDIES: The SUVs of delayed images from the known malignant lesions compared with those of earlier scans increased over time (+19.18% +/- 9.58%; n = 31; P < 0.001; 95% confidence interval, 15.8%-22.6%). By contrast, the SUVs of benign lung nodules decreased slightly over time (-6.3% +/- 8.1%; n = 12; P < 0.05; 95% confidence interval, -10.9% to -1.7%). The SUV of inflammatory lesions caused by radiation therapy (+1.16% +/- 7.23%; n = 8; P > 0.05; 95% confidence interval, -3.9%-6.2%) and the lesions of painful lower limb prostheses (+4.03% +/- 11.32%; n = 25; P > 0.05; 95% confidence interval, -0.4%-8.5%) remained stable over time. CONCLUSION: These preliminary data show that dual time imaging appears to be useful in distinguishing malignant from benign lesions. Further research is necessary to confirm these results.

Evaluation of recurrent squamous cell carcinoma of the head and neck with FDG positron emission tomography.

PURPOSE: This study compared the effectiveness of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT), magnetic resonance imaging (MRI), or both for the assessment of recurrent squamous cell carcinoma of the head and neck. The value of quantifying the standardized uptake values (SUV) to distinguish recurrent neoplasm from inflammatory lesions and normal structures was also evaluated. METHODS: Forty-three patients with head and neck cancer were examined with F-18 FDG PET at least 4 months after their last course of radiation therapy (mean, 11 months). The SUVs were measured in visually identified regions of abnormally increased activity and were compared with the values in normal mucosa, the base of the tongue, and the hard palate to determine if an optimal cutoff value exists for diagnosing recurrence of malignant lesions. The final diagnosis of recurrence was made based on biopsy or at least 6 months' clinical follow-up. RESULTS: FDG PET correctly detected recurrence in 20 of 22 patients who had 45 discrete lesions located in the field of the upper aerodigestive tract. Two false-negative and three false-positive results were identified. The accuracy of FDG PET was 88% (38 of 43 patients), compared with 66% (25 of 38 patients) for CT, MRI, or both. Although there was a significant difference of SUVs (P = 0.0036) between the recurrent lesions and normal structures, the optimal cutoff values were difficult to define. CONCLUSIONS: Visual analysis of FDG PET is significantly more accurate in the diagnosis of recurrent squamous cell cancer of the head and neck than are CT or MRI. However, single SUV quantification does not significantly enhance efficacy.

Gallbladder stone shown on a hepatobiliary scan.

Hepatobiliary scans are performed frequently to identify gallbladder-related disease. Although gallbladder stones are a common cause of hepatobiliary disease, they are visualized directly only rarely on hepatobiliary scans. Large gallbladder stones produced a photopenic defect in the gallbladder in a hepatobiliary scan.

Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography.

Quantification of dopamine transporters (DAT) using [99mTc]TRODAT-1 and single-photon emission tomography (SPET) requires full kinetic modeling of the data, using complex and invasive arterial blood sampling to provide an input function to the model. We have shown previously that a simpler reference tissue model provides accurate quantitative results, using a reference region devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop further simplifications to make the imaging protocol much more practical as a routine procedure. Fourteen healthy subjects (age 29.8 +/- 8.4 years, range 18.7-45.5 years) underwent dynamic SPET for 6 h following injection of 752 +/- 28 MBq [99mTc]TRODAT-1. The kinetic data were analyzed using nonlinear regression analysis (NLRA) and Logan-Patlak graphical analysis. In addition, simple average ratios of striatal-to-background counts were obtained for three 1-h periods (3-4 h, 4-5 h, 5-6 h), and compared against the kinetic models. All methods gave an index of specific binding, proportional to the binding potential, known as the distribution volume ratio (DVR). The reference tissue NLRA gave mean values of k3=0.013 +/- 0.003 min(-1), k4=0.011 +/- 0.002 min(-1), and DVR=2.29 +/- 0.17. Graphical analysis gave a value of DVR=2.28 +/- 0. 16, and the three ratio values of DVR were: 3-4 h, 2.18 +/- 0.15; 4-5 h, 2.34 +/- 0.13; and 5-6 h, 2.46 +/- 0.19. Graphical analysis was highly correlated with NLRA (R2=0.91, slope=0.90 +/- 0.08). The ratio methods correlated well with NLRA (3-4 h, R2=0.71, slope= 0.73 +/- 0.13; 4-5 h, R2=0.86, slope=0.73 +/- 0.09; 5-6 h, R2=0.80, slope=1.00 +/- 0.15), and also with graphical analysis (3-4 h, R2=0.65, slope=0.74 +/- 0.16; 4-5 h, R2=0.85, slope=0.78 +/- 0.09; 5-6 h, R2=0.88, slope=1.11 +/- 0.12). The optimum equilibrium time point for obtaining a simple ratio was approximately 4.5-5.5 h. In conclusion, the simple ratio techniques for obtaining a quantitative measure of specific binding correlated well with the reference tissue kinetic models, using both NLRA and graphical analysis. The optimum time for obtaining a ratio appeared to be in the range 4.5-5.5 h. Earlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations.

Regional cerebral distribution of [Tc-99m] hexylmethylpropylene amineoxine in patients with progressive aphasia.

Progressive aphasia is a prominent clinical feature of several neurodegenerative disorders. This study used hexylmethylpropylene amineoxine (HMPAO) single photon emission computed tomography (SPECT) to estimate blood flow in areas of the brain that mediate language in patients with progressive aphasia and matched control subjects. The patient population consisted of four men and 12 women with a mean +/- SD age of 69.1 +/- 7.6. Of these, eight were classified as having a nonfluent form of aphasia, whereas the other eight had a fluent form. The patients were compared to 16 healthy volunteers who were studied with an identical protocol. The SPECT images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m-labeled HMPAO on a triple-headed gamma camera equipped with fan beam collimators. The images were analyzed with a set of standardized templates. Mean counts per pixel in 33 regions of interest were compared to the mean counts in the whole supratentorial brain. A laterality index was determined for homotopic regions using the equation 100 x (R - L)/(1/2 x (R - L)). Patients with progressive aphasia had several regions of significantly decreased HMPAO uptake in the left cortex when compared to the homotopic regions on the right. The most prominent deficit in the nonfluent group, as determined by the laterality index, were found in the left dorsolateral prefrontal region (p < 0.05), whereas the most prominent deficits in the group with fluent aphasia were found in the left temporal and parietal language centers (p < 0.05). The left subcortical nuclei were differentially affected, particularly in patients with nonfluent aphasia. The HMPAO SPECT indicates that multiple regions of the left hemisphere are dysfunctional in patients with progressive aphasia. The pattern of perfusion deficits in patients with fluent aphasia appears to be distinct from the pattern in patients with nonfluent aphasia.

Regional cerebral glucose metabolism in healthy volunteers determined by fluordeoxyglucose positron emission tomography: appearance and variance in the transaxial, coronal, and sagittal planes.

PURPOSE: In this study, the contribution of the transaxial, coronal, and sagittal planes in evaluations of regional cerebral glucose metabolism was investigated in healthy volunteers as determined by fluorine-18-labeled 2-deoxy-2-fluoro-D-glucose (FDG) and high-resolution positron emission tomography (PET). METHODS: One hundred twenty-seven healthy right-handed volunteers were injected with 4.2 MBq/kg (0.11 mCi) body weight FDG and imaged in a PENN PET H 240 scanner. Images were corrected for scatter and random coincidences and reconstructed in all three planes into 6- to 8-mm-thick slices. The reconstructed images were corrected for attenuation using the Chang algorithm. The transverse, coronal, and sagittal images were read independently of each other using a qualitative scale in which 1 = equal to, 2 = mildly, 3 = moderately, and 4 = markedly less than the area with the highest glucose metabolism in the respective plane. RESULTS: The areas with the highest glucose metabolisms were the posterior cingulate gyri with mean scores of 1.1 to 1.2, thalami (1.2 to 1.3), basal ganglia (1.5 to 1.9), and visual cortex (1.6). The lowest values were found in the occipital cortex (2.7 to 2.8) and the cerebellum (2.3 to 2.4). Whereas reliable analysis of the mesial temporal aspects was not feasible in the sagittal plane, the anterior poles of the temporal and frontal lobes could not be evaluated in the coronal or the inferior temporal areas in the transaxial slices. In all three planes, regional glucose metabolism was less in the lateral temporal areas on the left than on the right (P < 0.001). The consistency of readings as measured in terms of coefficients of variation was greatest in the coronal plane for the caudates and posterior cingulate gyri, in the transaxial plane for the lateral temporal regions, and in the sagittal plane for the visual cortex. Age-dependent decreases in regional glucose metabolism in the inferior and lateral frontal regions and the parietal lobes were found in all three planes. CONCLUSIONS: All three projection planes must be used for a comprehensive qualitative evaluation of the regional glucose metabolism of the brain.

Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson's disease and in healthy volunteers.

UNLABELLED: [99mTc]TRODAT-1 is a radiolabeled tropane that binds dopamine transporters. The primary goal of this study was to determine whether its regional cerebral distribution could differentiate between patients with Parkinson's disease and healthy human volunteers. METHODS: The sample consisted of 42 patients with Parkinson's disease, 23 age-matched controls, and 38 healthy adults younger than 40 y old. SPECT scans of the brain were acquired on a triple-head gamma camera 3-4 h after the intravenous injection of 740 MBq (20 mCi) [99mTc]TRODAT-1. Mean counts per pixel were measured manually in subregions of the basal ganglia and normalized to the mean background counts to give specific uptake values ([SUVs] approximately k3/k4). Patient and control groups were also compared with automated statistical parametric mapping techniques. Logistic discriminant analyses were performed to determine the optimum uptake values for differentiating patients from age-matched controls. RESULTS: Quantitative image analysis showed that the group mean SUVs in patients were less than the mean values in controls for all regions (all Ps < 0.000001). There was overlap in the caudate as well as in the anterior-most portion of the putamen, but not in the posterior putamen, even when the asymptomatic sides of 5 patients with clinically defined hemi-Parkinson's disease were factored in. CONCLUSION: The findings indicate that Parkinson's disease can be detected with [99mTc]TRODAT by simply inspecting the images for uptake in the posterior putamen. Appropriate asymmetries seem to be visible with quantification in patients with clinically defined hemi-Parkinson's disease, even though changes in the putamen contralateral to the clinically unaffected side in these patients appear to precede the development of symptoms.

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis.

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.

Ipsilateral and contralateral thalamic hypometabolism as a predictor of outcome after temporal lobectomy for seizures.

UNLABELLED: FDG PET is often used to help localize the seizure focus before surgery in patients with medically refractory temporal lobe epilepsy. However, the ability of certain patterns of metabolic landscape to predict postsurgical seizure outcome has not been well characterized. The purpose of this retrospective study was to determine whether FDG PET abnormalities elsewhere in the brain, in combination with those in the temporal lobes, can be used to predict seizure outcome after surgery. METHODS: Eighty patients with refractory temporal lobe seizures were imaged with PET after intravenous administration of 115 microCi/kg FDG. Images were interpreted without knowledge of clinical information by an experienced reviewer to determine seizure focus and regional metabolic changes in the brain. Metabolic activity scores were assigned for cortical and subcortical structures using the following criteria: 4 = normal activity, 3 = mildly decreased activity, 2 = moderately decreased activity, 1 = severely decreased activity, and 0 = no activity. A laterality index for each region was calculated using the equation 100 x [right - left]/[1/2 x (right + left)]. Seizure focus localization was based on the laterality of temporal lobe metabolic activity and was compared with that determined by scalp and depth electrodes and MRI results. Comparisons were made between asymmetries in metabolic activity in various brain structures and postoperative seizure frequency. Postoperative outcome was determined on the basis of cessation (complete disappearance of seizures) or continuation of seizure activity, regardless of frequency, compared with the preoperative state. RESULTS: All 64 patients who were free of seizures postoperatively had either no thalamic asymmetry or reduced metabolism on the side from which the temporal lobe was removed. In contrast, 5 of 16 patients (31%) with postoperative seizures of any frequency had hypometabolism in the thalamus contralateral to that of the removed temporal lobe. All 5 patients with reverse thalamic asymmetry had postoperative seizures. Patients with thalamic hypometabolism ipsilateral to the removed temporal lobe also had an increased risk of postoperative seizures, but this risk was not as high as in patients with the contralateral abnormality. In these patients, the temporal lobe (which appeared hypometabolic on PET) was determined to be the site of the seizure on the basis of information besides that provided by PET before surgery. CONCLUSION: This study indicated that, in patients with temporal lobe epilepsy, thalamic metabolic asymmetry, particularly in the reverse direction to that of the temporal lobe asymmetry, was associated with a poor postsurgical outcome compared with no or matched asymmetry. This determination may be important in evaluating patients for, and selecting optimal candidates for, surgical intervention.

Single photon emission tomography imaging in parkinsonian disorders: a review.

Parkinsonian symptoms are associated with a number of neurodegenerative disorders, such as Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. Pathological evidence has shown clearly that these disorders are associated with a loss of neurons, particularly in the nigrostriatal dopaminergic pathway. Positron emission tomography (PET) and single photon emission tomography (SPECT) now are able to visualise and quantify changes in cerebral blood flow, glucose metabolism, and dopaminergic function produced by parkinsonian disorders. Both PET and SPECT have become important tools in the differential diagnosis of these diseases, and may have sufficient sensitivity to detect neuronal changes before the onset of clinical symptoms. Imaging is now being utilised to elucidate the genetic contribution to Parkinson's disease, and in longitudinal studies to assess the efficacy and mode of action of neuroprotective drug and surgical treatments. This review summarises recent applications of SPECT imaging in the study of parkinsonian disorders, with particular reference to the increasing role it is playing in the understanding, diagnosis and management of these diseases.