Biomedical subjects
Publications and source records attributed to J W Hugg.
A method is described for producing rapid diffusion-weighted images using a modified low flip angle imaging technique. Utility of the method is demonstrated by the quantification of diffusion coefficients in a rat model of focal ischemia. The method may be readily applied to animal research studies using NMR research systems with modest gradient capabilities.
Temporal lobe epileptogenic foci were blindly localized in 8 patients with medically refractory unilateral complex partial seizures using noninvasive in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) with 4-ml effective voxel size. The brain proton metabolite signals in 8 matched normal controls were bilaterally symmetrical within +/- 10%. The hippocampal seizure foci had 21 +/- 5% less N-acetyl aspartate signal than the contralateral hippocampal formations (p < 0.01). The focal N-acetyl aspartate reductions were consistent with pathology findings of mesial temporal sclerosis with selective neuron loss and gliosis in the surgically resected epileptogenic foci. Proton MRSI correctly localized the seizure focus in all 8 cases. By comparison, MR imaging correctly localized 7 of 8 cases and single photon emission computed tomography correctly localized 2 of 5 cases. No lactate was detected in these interictal studies. No significant changes in choline or creatine were observed. In conclusion, 1H-MRSI is a useful tool for the noninvasive clinical assessment of intractable focal epilepsy. These preliminary results suggest that 1H-MRSI can accurately localize temporal lobe epileptogenic foci.
A method for quantitation of in vivo 31P metabolite concentrations in human brain with 31P magnetic resonance spectroscopic imaging (MRSI) is described. The method relies on comparison of brain and calibration phantom measurements, with corrections for coil loading and metabolite magnetic relaxation. Estimated metabolite concentrations for the centrum semiovale in 11 normal adults (mean +/- SD) were: phosphomonoesters = 3.0 +/- 0.7 mM, inorganic phosphate = 0.7 +/- 0.2 mM, phosphodiesters = 10.9 +/- 1.8 mM, phosphocreatine = 2.7 +/- 0.5 mM, and adenosine triphosphate = 2.9 +/- 0.3 mM. These values are similar to previous results obtained from single-volume localized spectroscopy.
We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.
The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.
The goal of this study was to investigate lactate and pH distributions in subacutely and chronically infarcted human brains. Magnetic resonance spectroscopic imaging (MRSI) was used to map spatial distributions of 1H and 31P metabolites in 11 nonhemorrhagic subacute to chronic cerebral infarction patients and 11 controls. All six infarcts containing lactate were alkalotic (pHi = 7.20 +/- 0.04 vs. 7.05 +/- 0.01 contralateral, p less than 0.01). This finding of elevated lactate and alkalosis in chronic infarctions does not support the presence of chronic ischemia; however, it is consistent with the presence of phagocytic cells, gliosis, altered buffering mechanisms, and/or luxury perfusion. Total 1H and 31P metabolites were markedly reduced (about 50% on average) in subacute and chronic brain infarctions (p less than 0.01), and N-acetyl aspartate (NAA) was reduced more (approximately 75%) than other metabolites (p less than 0.01). Because NAA is localized in neurons, selective NAA reduction is consistent with pathological findings of a greater loss of neurons than glial cells in chronic infarctions.
Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.
Two-dimensional proton magnetic resonance (MR) spectroscopic imaging studies were performed of the distributions of the major hydrogen-1 metabolites of choline, creatine, N-acetyl aspartate (NAA) and lactate in normal (n = 6) and subacutely to chronically infarcted (n = 10) human brain. The two dimensions of phase encoding were applied over a 20-mm-thick section of brain tissue that had been selected with a double spin-echo localization method. Normal brain showed bilaterally symmetric metabolite distributions and no detectable lactate. Nine of 10 studies of brain infarction showed substantial decreases in NAA, creatine, and choline in the infarcted area compared with control areas; averaged for all studies, the decreases were 77% +/- 8, 63% +/- 11, and 54% +/- 12, respectively (mean +/- standard error). The decreased metabolite concentrations are probably due primarily to diminished cell density in the infarct. The decrease in NAA was larger than the decreases in choline and creatine. Findings in all of the studies showed lactate in the infarcted tissue and/or ventricles. The continued presence of lactate in the infarct indicates increased anaerobic glycolysis due to ischemia or other factors.
We attempted to lateralize the epileptogenic focus (seven temporal lobe hippocampal foci, one frontal lobe focus) in medically refractory unilateral complex partial seizures, using noninvasive 31P magnetic resonance spectroscopic imaging (MRSI) blindly and interictally to compare hippocampal or frontal regions. The seizure foci were more alkaline (intracellular pH = 7.17 +/- 0.03) compared with the contralateral region (7.06 +/- 0.02, p < 0.01) in all eight cases; the inorganic phosphate was relatively increased (240 +/- 50% of contralateral, seven of eight cases, p < 0.01); and phosphomonoesters were relatively reduced (68 +/- 9% of contralateral, seven of eight cases, p < 0.01). Other phosphorus metabolites were symmetric (+/- 10%). 31P MRSI correctly lateralized the seizure focus in all eight cases. By comparison, imaging correctly lateralized four cases and SPECT, two cases. In conclusion, 31P MRSI is a useful tool for the noninvasive clinical assessment of focal epilepsy and can accurately lateralize the epileptogenic focus.
Spectroscopic imaging of phosphorus metabolites in the human brain has been carried out with two data acquisition methods: by observation of the free induction decay (FID) signal and by a short spin echo sequence. The resultant spectral images and spatially resolved spectra are compared. Spin echo observation is found to provide spectra of superior quality, and by suitably selecting the sequence timing, no significant increase in T2 losses, as compared with the FID method, is encountered. 31P images with approximately 3.5 cm spatial resolution are obtained within times of 37 min at 2.0 T field strength.