cortical effects of white matter lesions identified by tc-99m hmpao spect

1
3-3 3-4 EVALUATION OF THE METABOLIC COMPONENTS OF THE STROKE PENUMBRA BY Te-99m HMPAO SPECT AND 4.1T 1H SPECTROSCOPY. James M. Moantz, M.D., Ph.D., G. Deutach, Ph.D., C. Inampudi, M.D., E. San Pedro, M.D., G. Mason, Ph.D., H. Hetherington, Ph.D., M. Mermemeier, Ph.D., J.S. Richards, Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL. Purpose: We performed rest/stress rCBF brain SPECT and high field (4.1T) NMR spectroscopy to characterize the components of the stroke penumbra. Methods: Ten patients with subacute stroke underwent Tc-99m HMPAO brain SPEC~ using a back- to-back low-dose(ras0 and high-dose(Diamox) protocol on the ADAC Genesys. rCBF data analysis was performed by comparing perfusion defect volumes to MRI defect volumes. IH brain metabolites (NAA, lactate, choline, crentine) were measured in whole brain sections through the stroke. Results: The penumbra can be characterized by three predominant components. Patients with no change in the size of the rest/stress SPECT defect volume (n=4) had abnormal 1H-metabolites only at the infarction rim. Patients with an increase in the stress/rest SPECT defect volume size (n--4) showed abnormal levels of lH-metubolites distant from the stroke tim indicating the presence of ischemia. Patients with a decrease in the stress/rest SPECT defect volume size (n=2) had normal lH-metabolites distant from the stroke rim indicating the presence of diaschisis. Conclusions: The stroke penumbra can be characterized by differentiating it's functional components into ischemia, diaschiais, or selective neuronal loss. This characterization is important in patient rehabilitation management. CORTICAL EFFECTS OF WHITE MATTER LESIONS IDENTIFIED BY Tc-99m HMPAO SPECT. James M. Mountz. M.D.. Ph.D., G. Deutsch, Ph.D., E. San'Pedro, M.D., H.G, Lin, M.S., L.E. Harrell, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL. Purpose: White matter hyper-intensities are often reported and attributed to factors such as iscbemia and small vessel "microangiopathy." We report on the regional cortical blood flow (rCBF) effects of such lesions and potential confounds with Alzheimer's disease (AD). Methods: Patients were a subset of 160 patients referred for brain SPECT by the UAB Memory Clinic. SPECT scanning was performed on the ADAC Genesis gamma camera. A reference system that generated external point images allowed accurate alignment and fusion of SPECT and MRI slices, rCBF pattums were plotted as cortical circumferential profiles and compared to normal data. Results: 36 patients had white matter hyper-intenaities on TT-weighted MPd. Overlaying images revealed a relationship between the rCBF defect and density of lucencies in adjacent regions. A more general rCBF impairment was also evident across the group: a posterior frontal reduction, involving 5-10% of the cortical rim, not typical of mild/moderate AD or any vascular territorial insufficiency. Clinical symptoms suggested more "frontal" impairments than in typical AD. Conclusion: SPECT is thus capable of identifying situations in which dementia symptoms arise from cortical activity reduction that is a secondary consequence of microangiopathy as opposed to AD. This form of dementia appears to be more prevalent than previously suspected. 3-5 3-6 A NEW PERSONAL COMPUTER BASED METHOD FOR CORRELATION OF SPECT OR PET WITH CT OR MRI. Bin Zhang, M.S., H.O. Liu, M.S., J.M. Monntz, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, Alabama. Purpose: Due to the lack of common image platforms, anatomic scans are not routinely co- registered with functional scans. We report the results of PC based software which has a capability of co-registration on a IBM PC platform. Methods: The hardware has been previously described (Comput Med tmag Graph 18:163-174, 1994). Using visual BASIC and C++ a program was written t~ co-register the fiduciary points on all axial sections of the anatomic and functional scans to provide a aide-by-side co-registered display, or fusion images. The software package also converts multiple image file formats (e.g. GE, ADAC Pegasys, Odyssey, Philips, etc.). The software automatically finds the reference vectors, calculates the transformation matrix, and displays co-registered images. Results: The average repoaitioning error of the hardware on patients between MRI and SPECT was ±2* which translates into a maximum anterior deviation of 2ram (the size of one SPECT pixel). The error in calculating the vector position by the program is much smaller (<0.77°, 0.67ram). Conclusion: The PC based co-registration system allows universal utilization of this accurate reference system in the routine clinical setting, independent of the users type of anatomic or functional imaging systems. PROTON MAGNETIC RESONANCE SPECTROSCOPY IN METACHROMATIC LEUKODYSTROPHY, A. Aria Tzlka Ph.D., Bail, Jr., M.D., Franz, M.D., Sambrano, M.D., Children's Hospital and Harvard Medical School, Boston, MA Puroose: To evaluate proton magnetic resonance spectroscopy (MRS) in childhood metachromatic leukodystrophy {MLD), a genetic neurological disease inherited in an autosomal recessive pattern that affects brain myelin. Methods: Six children, three of which were 16 +9 months old and three 6 +_ 2.5 years old, of parents with MLD trait had MRS. Both parents of these children were also studied with MRS and compared with healthy adults. MRS was performed using single voxel stimulated echoes (TR = 2 sec; TE = 20-30 ms) on a 1.5 T system. N-acetylaspartate (NAA), choline-containing compounds (Cho) and inositola (Inls) peak areas were divided by the total creatine (tCr area). Results: The younger children had mean values for: NAA/tCr = 1.47; Cho/tCr = 1.03; Inls/tCr = 1.72 and the older 1.30; 0.70; 1.51 respectively. The only metabolite ratio which was significantly increased in both younger and older children and their MLD parents was Inls/tCr. Conclusions: The "glial marker" peak, Inls, seems to be affected in MLD parents and. their children as shown by MRS. 3-7 3-8 CEREBROVASCR/LAR STRESS TESTS IN PARENCI-IYMAL VERSUS VASCUI#~ CEREBRAL DISEASE. Georg Dantsch, Ph.D., J.M. Mountz, M.D., Ph.D., H-G. Liu, M.S., E. San Pedro, M.D., University of Alabama at Birmingham Medical Center, Birmingham, AL. Purpo~: Regional cerebral blood flow (rCBF) reactivity to vasodilatoss such as CO2 or acetazolamide is typically used to accentuate vascular supply problems. Our studies are extending the use of such cerebral stress tests to separating primary neurometabolie from vascular dysfunction in stroke and dementia. Methods: Three patient groups were studied with dual state, rest (baseline) and stress, rCBF scans: 30 with Alzheimer's disease (AD), I0 patients three weeks post stroke, and 10 patients one year post stroke, rCBF was measured by 99m-Tc HMPAO SPECT or 133-Xe clearance. Results: In AD, baseline rCBF was most reduced in parietal-temporal regions, but this increased dramatically during elevated CO 2. Early stage stroke patients typically showed rCBF impairments exceeding the infarct volume at rest that then paradoxically "improved" during stress. Chronic stage stroke patients had rCBF impairments confined to the infarct volume with minimal changes during stress. Conclusions: The anomalously high reactivity in AD represents a situation in which baseline rCBF reductions reflect pure paranehymal neurometabolic disease without vascular constraint. A parallel, but temporary, phenomenon occurs in the peri-infarot region post stroke, where we hypothesize baseline rCBF is reduced secondary to neuronal disconnection effects (diaachisis), and stress tests reverse the abnormality. Stress test reversal thus identifies "stunned" puranchyma post stroke, IN VIVO DETECTION OF BRAIN PROPYLENE GLYCOL BY PROTON MR SPECTROSCOPY, McConnell. J.R., tug, C.S.; Gross, T.G.; McAllister, I.L., University of Nebraska Medical Center, Omaha, NE Purpose: Investigation of pathologic metabolism in children by in vivo brain proton MR spectroscopy (IH MRS). Methods: In vivo and in vitro IH MRS were done with a 1.5 Tesla clinical imager using single voxel technique and the PRESS sequence; TR-2s, TE-40, 135, 270 ms. The in vitro sample contained 5mM of propylene glycol (PG) and 5mM of lactate (Lac) as a chemical shift reference at 1.3 ppm. Results: Four patients in the study group were found to have an unexpected doublet signal at 1.1 ppm Case I had encephalitis, seizures and lactic acidosis. Case 2 had severe hypoxic encephalopathy, seizures and liver/lddney failure. Case 3 had mild encephaiopathy after bone marrow transplant. Case 4 bad mild birth asphyxia and seizures. These cases were being treated with various drugs containing PG. The doublet at 1. I ppm on the in vivo brain spectra was identified as the PG methyl protons. Conclusion: PG is a solvent vehicle for many different drugs. It's usually considered non-toxic, but there are reports that it can cause hyperosmolaiity, lactic acidosis, hemolysis and renal failure. In vivo IHMRS can be used to assess brain PG and may be useful in the investigation of its toxicity and neurochemistry.

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Page 1: Cortical effects of white matter lesions identified by Tc-99m HMPAO spect

3-3 3-4

EVALUATION OF THE METABOLIC COMPONENTS OF THE STROKE PENUMBRA BY Te-99m HMPAO SPECT AND 4.1T 1H S P E C T R O S C O P Y . James M. Moantz, M.D., Ph.D., G. Deutach, Ph.D., C. Inampudi, M.D., E. San Pedro, M.D., G. Mason, Ph.D., H. Hetherington, Ph.D., M. Mermemeier, Ph.D., J.S. Richards, Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL.

Purpose: We performed rest/stress rCBF brain SPECT and high field (4.1T) NMR spectroscopy to characterize the components of the stroke penumbra. Methods: Ten patients with subacute stroke underwent Tc-99m HMPAO brain SPEC~ using a back- to-back low-dose(ras0 and high-dose(Diamox) protocol on the ADAC Genesys. rCBF data analysis was performed by comparing perfusion defect volumes to MRI defect volumes. IH brain metabolites (NAA, lactate, choline, crentine) were measured in whole brain sections through the stroke. Results: The penumbra can be characterized by three predominant components. Patients with no change in the size of the rest/stress SPECT defect volume (n=4) had abnormal 1H-metabolites only at the infarction rim. Patients with an increase in the stress/rest SPECT defect volume size (n--4) showed abnormal levels of lH-metubolites distant from the stroke tim indicating the presence of ischemia. Patients with a decrease in the stress/rest SPECT defect volume size (n=2) had normal lH-metabolites distant from the stroke rim indicating the presence of diaschisis. Conclusions: The stroke penumbra can be characterized by differentiating it's functional components into ischemia, diaschiais, or selective neuronal loss. This characterization is important in patient rehabilitation management.

C O R T I C A L EFFECTS OF W H I T E M A T T E R LESIONS IDENTIFIED BY Tc-99m HMPAO SPECT. James M. Mountz. M.D.. Ph.D., G. Deutsch, Ph.D., E. San'Pedro, M.D., H.G, Lin, M.S., L.E. Harrell, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL.

Purpose: White matter hyper-intensities are often reported and attributed to factors such as iscbemia and small vessel "microangiopathy." We report on the regional cortical blood flow (rCBF) effects of such lesions and potential confounds with Alzheimer's disease (AD). Methods: Patients were a subset of 160 patients referred for brain SPECT by the UAB Memory Clinic. SPECT scanning was performed on the ADAC Genesis gamma camera. A reference system that generated external point images allowed accurate alignment and fusion of SPECT and MRI slices, rCBF pattums were plotted as cortical circumferential profiles and compared to normal data. Results: 36 patients had white matter hyper-intenaities on TT-weighted MPd. Overlaying images revealed a relationship between the rCBF defect and density of lucencies in adjacent regions. A more general rCBF impairment was also evident across the group: a posterior frontal reduction, involving 5-10% of the cortical rim, not typical of mild/moderate AD or any vascular territorial insufficiency. Clinical symptoms suggested more "frontal" impairments than in typical AD. Conclusion: SPECT is thus capable of identifying situations in which dementia symptoms arise from cortical activity reduction that is a secondary consequence of microangiopathy as opposed to AD. This form of dementia appears to be more prevalent than previously suspected.

3-5 3-6

A NEW PERSONAL COMPU TER BASED METHOD FOR C O R R E L A T I O N OF SPECT OR PET WITH CT OR MRI. Bin Zhang, M.S., H.O. Liu, M.S., J.M. Monntz, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, Alabama.

Purpose: Due to the lack of common image platforms, anatomic scans are not routinely co- registered with functional scans. We report the results of PC based software which has a capability of co-registration on a IBM PC platform. Methods: The hardware has been previously described (Comput Med tmag Graph 18:163-174, 1994). Using visual BASIC and C++ a program was written t~ co-register the fiduciary points on all axial sections of the anatomic and functional scans to provide a aide-by-side co-registered display, or fusion images. The software package also converts multiple image file formats (e.g. GE, ADAC Pegasys, Odyssey, Philips, etc.). The software automatically finds the reference vectors, calculates the transformation matrix, and displays co-registered images. Results: The average repoaitioning error of the hardware on patients between MRI and SPECT was ±2* which translates into a maximum anterior deviation of 2ram (the size of one SPECT pixel). The error in calculating the vector position by the program is much smaller (<0.77 °, 0.67ram). Conclus ion: The PC based co-registration system allows universal utilization of this accurate reference system in the routine clinical setting, independent of the users type of anatomic or functional imaging systems.

PROTON MAGNETIC RESONANCE S P E C T R O S C O P Y IN METACHROMATIC LEUKODYSTROPHY, A. Ar ia T z l k a Ph .D. , Bai l , J r . , M.D. , F ranz , M.D. , S a m b r a n o , M.D., C h i l d r e n ' s H o s p i t a l a n d H a r v a r d Med ica l School , Bos ton , MA

P u r o o s e : To e v a l u a t e p r o t on m a g n e t i c r e s o n a n c e s p e c t r o s c o p y (MRS) in c h i l d h o o d m e t a c h r o m a t i c l e u k o d y s t r o p h y {MLD), a gene t i c n e u r o l o g i c a l d i s e a s e i n h e r i t e d in a n a u t o s o m a l r e c e s s i v e p a t t e r n t h a t a f fec t s b r a i n mye l in .

Me t hods : S ix ch i l d r en , t h r e e o f w h i c h w e r e 16 + 9 m o n t h s old a n d t h r e e 6 +_ 2 . 5 y e a r s old, of p a r e n t s w i t h MLD t r a i t h a d MRS. B o t h p a r e n t s o f t h e s e c h i l d r e n were a l so s t u d i e d w i t h MRS a n d c o m p a r e d w i t h h e a l t h y adu l t s . MRS w a s p e r f o r m e d u s i n g s ingle voxel s t i m u l a t e d echoes (TR = 2 sec; T E = 2 0 - 3 0 ms) on a 1.5 T sys t em. N - a c e t y l a s p a r t a t e (NAA), c h o l i n e - c o n t a i n i n g c o m p o u n d s (Cho) a n d inos i to la (Inls) p e a k a r e a s w e r e d iv ided by t h e to t a l c r e a t i n e (tCr a rea) .

Resu l t s : T h e y o u n g e r c h i l d r e n h a d m e a n v a l u e s for: N A A / t C r = 1.47; C h o / t C r = 1.03; I n l s / t C r = 1 .72 a n d t h e o lde r 1 .30; 0 . 7 0 ; 1 .51 respec t ive ly . The only m e t a b o l i t e r a t io w h i c h w a s s ign i f i can t ly i n c r e a s e d in b o t h y o u n g e r a n d o lde r c h i l d r e n a n d t h e i r MLD p a r e n t s w a s I n l s / t C r .

C o n c l u s i o n s : T h e "glial m a r k e r " p e a k , In ls , s e e m s to be a f fec ted in MLD p a r e n t s a n d . t h e i r c h i l d r e n a s s h o w n by MRS.

3-7 3-8

CEREBROVASCR/LAR STRESS TESTS IN PARENCI-IYMAL VERSUS V A S C U I # ~ C E R E B R A L DISEASE. Georg Dantsch, Ph.D., J.M. Mountz, M.D., Ph.D., H-G. Liu, M.S., E. San Pedro, M.D., University of Alabama at Birmingham Medical Center, Birmingham, AL.

Purpo~: Regional cerebral blood flow (rCBF) reactivity to vasodilatoss such as CO2 or acetazolamide is typically used to accentuate vascular supply problems. Our studies are extending the use of such cerebral stress tests to separating primary neurometabolie from vascular dysfunction in stroke and dementia. Methods: Three patient groups were studied with dual state, rest (baseline) and stress, rCBF scans: 30 with Alzheimer's disease (AD), I0 patients three weeks post stroke, and 10 patients one year post stroke, rCBF was measured by 99m-Tc HMPAO SPECT or 133-Xe clearance. Results: In AD, baseline rCBF was most reduced in parietal-temporal regions, but this increased dramatically during elevated CO 2. Early stage stroke patients typically showed rCBF impairments exceeding the infarct volume at rest that then paradoxically "improved" during stress. Chronic stage stroke patients had rCBF impairments confined to the infarct volume with minimal changes during stress. Conclusions: The anomalously high reactivity in AD represents a situation in which baseline rCBF reductions reflect pure paranehymal neurometabolic disease without vascular constraint. A parallel, but temporary, phenomenon occurs in the peri-infarot region post stroke, where we hypothesize baseline rCBF is reduced secondary to neuronal disconnection effects (diaachisis), and stress tests reverse the abnormality. Stress test reversal thus identifies "stunned" puranchyma post stroke,

IN VIVO DETECTION OF BRAIN PROPYLENE GLYCOL BY PROTON MR SPECTROSCOPY, McConnell. J.R., tug , C.S.; Gross, T.G.; McAllister, I.L., University of Nebraska Medical Center, Omaha, NE Purpose: Investigation of pathologic metabolism in children by in vivo brain proton MR spectroscopy (IH MRS). Methods: In vivo and in vitro IH MRS were done with a 1.5 Tesla clinical imager using single voxel technique and the PRESS sequence; TR-2s, TE-40, 135, 270 ms. The in vitro sample contained 5mM of propylene glycol (PG) and 5mM of lactate (Lac) as a chemical shift reference at 1.3 ppm. Results: Four patients in the study group were found to have an unexpected doublet signal at 1.1 ppm Case I had encephalitis, seizures and lactic acidosis. Case 2 had severe hypoxic encephalopathy, seizures and liver/lddney failure. Case 3 had mild encephaiopathy after bone marrow transplant. Case 4 bad mild birth asphyxia and seizures. These cases were being treated with various drugs containing PG. The doublet at 1. I ppm on the in vivo brain spectra was identified as the PG methyl protons. Conclusion: PG is a solvent vehicle for many different drugs. It's usually considered non-toxic, but there are reports that it can cause hyperosmolaiity, lactic acidosis, hemolysis and renal failure. In vivo IHMRS can be used to assess brain PG and may be useful in the investigation of its toxicity and neurochemistry.