A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson's disease.

Although [(18)F]fluoro-L: -dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function.

Rate of 6-[18F]fluorodopa uptake decline in striatal subregions in Parkinson's disease.

BACKGROUND: Rate of decline in 6-L-[(18)F]fluorodopa (FDOPA) uptake within the striatum has been reported as showing regional differences in Parkinson's disease (PD). METHODS: We acquired longitudinal brain FDOPA positron emission tomography (PET) studies in 26 PD subjects and 11 controls over 4.5 years. We analyzed both spatially normalized voxel-wise maps of radiotracer influx (Kocc) and average Kocc values for six non-overlapping volumes of interest (VOIs) encompassing the striatum. RESULTS: The voxel-wise analysis showed that in PD, FDOPA Kocc decline spanned the striatum but was greatest in the posterior putamen ipsilateral and anterior putamen contralateral to initial symptoms. The VOI approached showed that absolute rates of Kocc decline were significantly greater in PD than control subjects, but that the slope of decline did not differ between subregions. In PD, ratios of uptake between subregions did not change during the study with the exception of the ipsilateral putamen/caudate ratio. Decline rates were marginally greater during earlier time segments. Both male gender and advancing age were associated with lower baseline FDOPA uptake, but no difference in decline rates. VOI Kocc values were significantly correlated with disease duration, but only moderately correlated with clinical measures. DISCUSSION: We conclude that FDOPA uptake in subregions of the striatum is strongly correlated with disease duration and age, and declines approximately equally from symptom onset in PD. This implies that in idiopathic PD, relative preservation of uptake in the anterior striatum reflects a delay in pathologic involvement of nigrostriatal projections to this region.

Potential of magnetization transfer MRI for target volume definition in patients with non-small-cell lung cancer.

PURPOSE: To develop a magnetization transfer (MT) module in conjunction with a single-shot MRI readout technique and to investigate the MT phenomenon in non-small-cell lung cancer (NSCLC) as an adjunct for radiation therapy planning. MATERIALS AND METHODS: A total of 10 patients with inoperable NSCLC were investigated using a 1.5T MR scanner. MT ratio (MTR) maps of several slices throughout the tumor were assessed. Each MTR-map was acquired within a short breathhold. Fluorodeoxyglucose positron emission tomography (FDG-PET) investigations were performed in addition to the MRI protocol. A total of 60 structures appearing conspicuous in FDG-PET were compared with structures appearing conspicuous in corresponding MTR maps. Quantification of similarity between both modalities was performed using similarity index calculation. RESULTS: MTR-maps showed different contrast than FDG-PET images. However, structures that appeared conspicuous in FDG-PET images, either by a marked signal enhancement or signal decrease, were found to be similarly present in MTR maps. A mean similarity index of 0.65 was calculated. MTR values of suspected atelectasis were on average lower than MTR values of tumor tissue. CONCLUSION: The proposed MT-MRI technique provides a high MT efficiency, while being robust and fast enough for breathhold acquisition. The results obtained encourage for further exploration of MT-MRI as an adjunct for radiotherapy planning in NSCLC.

Memory for famous faces and the temporal pole: functional imaging findings in temporal lobe epilepsy.

The ability to recognize, name, and provide information about famous persons is deficient in patients with temporal lobe epilepsy (TLE), although the neural basis for these deficits is not well understood. We examined the relationship of resting metabolism of the temporal poles, as determined by [18F] fluorodeoxyglucose positron emission tomography, to performance on a task of famous face recognition, naming, and generation of semantic information in 12 patients with TLE. Correlations between metabolic measures of the temporal poles and performance on the Famous Faces Task revealed strong relationships between all aspects of the Famous Faces Task and the left temporal pole, whereas Famous Faces Task correlations with the right temporal pole were not significant. These findings indicate that the left temporal pole is associated with lexical and semantic retrieval of knowledge of famous persons in patients with TLE. Further study appears warranted to elucidate the networks involved in semantic knowledge for famous faces.

Noninvasive mapping of regional response to segmental allergen challenge using magnetic resonance imaging and [F-18]fluorodeoxyglucose positron emission tomography.

Magnetic resonance (MR) and positron emission tomography (PET) imaging techniques were coregistered to demonstrate regional ventilation and inflammation in the lung for in vivo, noninvasive evaluation of regional lung function associated with allergic inflammation. Four Brown Norway rats were imaged pre- and post segmental allergen challenge using respiratory-gated He-3 magnetic resonance imaging (MRI) to visualize ventilation, T(1)-weighted proton MRI to depict inflammatory infiltrate, and [F-18]fluorodeoxyglucose-PET to detect regional glucose metabolism by inflammatory cells. Segmental allergen challenges were delivered and the pre- and postchallenge lung as well as the contralateral lung were compared. Coregistration of the imaging results demonstrated that regions of ventilation defects, inflammatory infiltrate, and increased glucose metabolism correlated well with the site of allergen challenge delivery and inflammatory cell recruitment, as confirmed by histology. This method demonstrates that fusion of functional and anatomic PET and MRI image data may be useful to elucidate the functional correlates of inflammatory processes in the lungs.

The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse.

A developmental role for the Ahr locus has been indicated by the observation that mice harboring a null allele display a portocaval vascular shunt throughout life. To define the ontogeny and determine the identity of this shunt, we developed a visualization approach in which three-dimensional (3D) images of the developing liver vasculature are generated from serial sections. Applying this 3D visualization approach at multiple developmental times allowed us to demonstrate that the portocaval shunt observed in Ahr-null mice is the remnant of an embryonic structure and is not acquired after birth. We observed that the shunt is found in late-stage wild-type embryos but closes during the first 48 h of postnatal life. In contrast, the same structure fails to close in Ahr-null mice and remains open throughout adulthood. The ontogeny of this shunt, along with its 3D position, allowed us to conclude that this shunt is a patent developmental structure known as the ductus venosus (DV). Upon searching for a physiological cause of the patent DV, we observed that during the first 48 h, most major hepatic veins, such as the portal and umbilical veins, normally decrease in diameter but do not change in Ahr-null mice. This observation suggests that failure of the DV to close may be the consequence of increased blood pressure or a failure in vasoconstriction in the developing liver.

Memory relationships between MRI volumes and resting PET metabolism of medial temporal lobe structures.

Prior studies of temporal lobe epilepsy (TLE) patients showed that MRI volumes and resting PET scan measures of temporal lobe structures were related to memory. Weintrob and colleagues [Ann. Neurol. 2002;51:442-7] reported that PET glucose uptake in the left perirhinal cortex predicted verbal paired associate (PA) learning, whereas MRI volume of the left hippocampus did not. We investigated whether MRI volumes could account for memory functioning if both PET and volumes were from the same region in 18 TLE patients. Volumes and glucose uptake of the hippocampus and parahippocampal gyrus (PHG) were compared with WMS-III performance. Significant correlations were observed between hippocampal volumes and PA and Logical Memory (LM) Percent Retention, but not between memory and PHG volumes or any PET measures. Multiple regression revealed that hippocampal volumes, but not PHG volumes or PET, significantly predicted PA and LM retention scores. These findings suggest that hippocampal volumes provide unique information regarding memory.

A controlled quantitative MRI volumetric investigation of hippocampal contributions to immediate and delayed memory performance.

MRI volumetric TLE studies show inconsistent evidence of hippocampal involvement in memory. Prior studies have not dissociated hippocampal and temporal lobe contributions to memory. We measured hippocampal and temporal lobe volumes and immediate/delayed memory performances in 64 TLE patients. Regression was used to dissociate hippocampal from temporal lobe contributions to memory. Results revealed reliable evidence for dominant hippocampal involvement in delayed verbal recall across three separate measures and less consistent evidence for nondominant hippocampal involvement. The findings point to a consistent relationship of dominant hippocampal volumes to delayed verbal recall but no involvement of the temporal lobe or nondominant hippocampus in memory.

Whole-body positron emission tomography in patients with HIV-1 infection.

Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) detects active lymphoid tissues during HIV-1 infection in man. We used FDG-PET to study anatomical correlates of HIV-1 infection in man. Whole-body FDG-PET images from 15 patients with HIV-1 showed distinct lymphoid tissue activation in the head and neck during acute disease, a generalised pattern of peripheral lymph-node activation at mid-stages, and involvement of abdominal lymph nodes during late disease. Unexpectedly, HIV-1 progression was evident by distinct anatomical correlates, suggesting that lymphoid tissues are engaged in a predictable sequence. Understanding the anatomy of HIV-1 infection could encourage use of surgical or radiological interventions to supplement chemotherapy.