Case control study of diffusion tensor imaging in Parkinson's disease.

BACKGROUND: Preliminary work has shown that diffusion tensor MRI (DTI) may contribute to the diagnosis of Parkinson's disease (PD). OBJECTIVES: We conducted a large, prospective, case control study to determine: (1) if fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls; and (2) the predictive value of these parameters and their clinical utility. METHODS: DTI imaging was carried out in patients with PD and controls. FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard. The structures studied were: caudate, putamen, globus pallidus, thalamus and substantia nigra. RESULTS: 151 subjects (73 PD patients, 41 men, 32 women; mean age 63.6 years) and 78 age and sex matched control subjects were studied. The FA value of the substantia nigra in patients with PD was lower compared with controls (0.403 vs 0.415; p = 0.001). However, no significant differences were demonstrated for FA or ADC values of other structures. Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD (regression coefficient -0.019). No single FA value had both a high positive and negative predictive power for PD. CONCLUSIONS: We demonstrated in a large, prospective, case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls, and correlated inversely with the clinical severity of PD. Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response.

Synaptic localization and restricted diffusion of a Drosophila neuronal synaptobrevin--green fluorescent protein chimera in vivo.

Fluorescent markers for subcellular compartments in Drosophila neurons should allow one to combine genetic mutant analysis with visualization of subcellular structures in vivo. Here we describe an analysis of two markers which may be used to observe different compartments of live Drosophila synapses. Soluble jellyfish green fluorescent protein (GFP) expressed at high levels in neurons diffuses freely in the neuronal cytosol as evidenced by confocal microscopy and fluorescence recovery from photobleaching experiments. Thus, the distribution pattern of soluble GFP in motor axons and larval motor terminals indicates the expected distribution for diffusible presynaptic molecules. In contrast to GFP, a neurally expressed neuronal synaptobrevin-GFP chimera (n-syb GFP) is transported down axons and specifically localized to nerve terminals. We demonstrate that n-syb GFP labels synaptic-vesicle membrane at larval motor terminals by documenting its restriction to presynaptic varicosities, its colocalization with synaptic vesicle antigens, and its redistribution in Drosophila shits1 mutant nerve terminals transiently depleted of synaptic vesicles. Surprisingly, n-syb GFP expressed in muscle is concentrated at the subsynaptic reticulum (SSR), postsynaptic infoldings of muscle plasma membrane. We suggest, using different membrane markers, that this apparent postsynaptic enrichment simply reflects a concentration of plasma membrane in the SSR, rather than a selective targeting of n-syb GFP to postsynaptic sites. Utilities and implications of these studies are demonstrated or discussed.

Temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma: 1H MR spectroscopic findings.

PURPOSE: To observe the patterns of radiation-induced temporal lobe necrosis (TLN) following radiation therapy for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty-five proton magnetic resonance spectroscopic (1H MRS) examinations were acquired from 13 healthy adult volunteers for comparison with data from the patient population. There were 18 patients (28 spectra) with radiologic evidence of TLN and all patients were confirmed cases of NPC treated with radiation therapy. Six patients (33%) had a single treatment while 12 (67%) patients had two treatments. All 1H MRS examinations were performed on a 2-T whole body system (Bruker) using the point-resolved spectroscopy (PRESS) method with TE = 135 ms, TR = 3000 ms, and data processed automatically using the LCModel software package for metabolite quantification. RESULTS: The N-acetyl-aspartate (NAA) levels were reduced in all except one spectrum (96%). Choline (Cho) was increased in 3 (11%), normal in 4 (14%), and reduced in 21 (75%) spectra. The creatine (Cr) level was normal in 8 (29%) spectra and reduced in 20 (71%) spectra. In four patients with normal imaging findings 1H MRS was abnormal. CONCLUSION: 1H MRS can characterize radiation-induced TLN. Spectra with increased Cho can be mistaken for neoplasm. Spectroscopy can also identify metabolic derangement before imaging.