Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2000-10-17
2001-07-10
Henley, III, Raymond (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S263370
Reexamination Certificate
active
06258794
ABSTRACT:
BACKGROUND
Major depression has been associated with both global and regional decreases in cerebral blood flow and glucose metabolism, assessed using emission tomography methods (reviewed in 1). In parallel, single voxel phosphorus-31 MRS has been used to document decreased levels of beta and total NTP in the basal ganglia (2; −16% and −6%) and the bilateral frontal lobes (3; −17% and −8%). Although these results are somewhat surprising, they are consistent with observations obtained from the cerebral cortex of polysubstance abusers (5; −10% and −7%) and decline in beta NTP in the basal ganglia of schizophrenics (4; −11%), disorders which have also been associated with sustained cerebral hypometabolism.
Over the last several years, van Zijl and colleagues (6,7,8) have clearly demonstrated that a
1
H MRS resonance which arises from purines may be detected in the range 7.8-8.8 PPM using short echo times. This resonance arises primarily from adenosine phosphates, with a smaller contribution from NAA at 7.8-8.0 PPM.
SUMMARY
We have reanalyzed the low field purine resonance in short echo time STEAM spectra acquired from the basal ganglia of depressed and healthy subjects (9). As a subset of these subjects also participated in a
31
P MRS study (2), the relationship between the
1
H MRS purine-resonance and the
31
PNTP resonance was assessed. Finally, as all of the depressed study subjects were enrolled in a standardized clinical trial,
1
H MRS purine measures were correlated with the clinical response to treatment.
All MR spectra were obtained using a GE Signa 1.5T MR scanner (4.8 operating system). Proton spectra were acquired from an 8 cm
3
voxel centered the left caudate and putamen. STEAM acquisition parameters were TR=2 sec., THE=30 msec., 256 averages, 1024 data points, and 2500 Hz spectral width. Phosphorus-31 spectra were acquired from a 45 cm
3
volume encompassing the bilateral basal ganglia. ISIS acquisition parameters were TR=3 sec., flip angle=90 degrees, acquisition delay=350 microsec, 512 averages, 1024 data points, and 2500 Hz spectral width. All subjects completed the
1
H MRS protocol while 13 depressed and 18 control subjects completed the
31
P MRS study.
Spectra were analyzed using SA/GE (described in 2 and 9) by a single analysis who was blind to clinical data. The intensity of the purine resonance was determined by integration of the 7.53-8.52 PPM region and separately normalized to the intensity of the resonances for NAA, Cre, and Cho. Images used for voxel prescription were segmented into gray matter, white matter, and CSF using MRX
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Henley III Raymond
The McLean Hospital Corporation
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