Spectroscopic assessment of alterations in macromolecule and small-molecule metabolites in human brain after stroke.

BACKGROUND AND PURPOSE: We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate, N-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy. METHODS: Single-voxel spectra with TE=22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients. RESULTS: Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased N-acetyl compounds were closely correlated in the 2D spectroscopic images. CONCLUSIONS: Short echo time spectra can be acquired in vivo in a manner that improves signal-to-noise ratio over long echo experiments and resolves overlapping macromolecule and small-molecule signals. The prominent macromolecule signals seen in the subacute period in association with persistently elevated lactate may represent mobile lipids in macrophages or other cells.

Influence of clostridial vaccines and injection sites on performance, feeding behavior, and lesion size scores of beef steers.

Several clostridial vaccines are currently being used in the beef cattle industry. Of greatest concern is altering the location and route of administration of these vaccines to reduce injection-site lesions while maintaining seroconversion. Two experiments were conducted to determine the effect of clostridial vaccines and injection sites on the performance, feeding behavior, and lesion size scores of beef steers. In Exp. 1, 80 crossbred beef steers (BW 237 +/- 3.2 kg) were allotted randomly into five groups and given 14 d to adapt to the feed and individual feed intake-monitoring devices (Pinpointer devices) before starting the study. Each group was assigned randomly to one of the following vaccination treatments: 1) control (sterile saline water), 2) Alpha-7 Ear (A7E), 3) Alpha-7 Prescapula (A7P), 4) Vision-7 Prescapula (V7P), and 5) Ultrabac-7 Prescapula (U7P). All vaccines were injected s.c. in the ear or prescapular region, and injection sites were palpated on d 0 and 28 (Exp. 1) and on d 63 and 91 (Exp. 2). The protocol for Exp. 2 was exactly the same as for Exp. 1 except treatments included control, A7P, Alpha-CD Ear (ACDE), Alpha-CD Prescapula (ACDP), Fortress-7 Prescapula (F7P), and V7P. Also, control and steers receiving F7P and V7P were revaccinated on d 63 and palpated on d 91. Results of Exp. 1 indicated that the A7E and U7P steers had a feed intake lower (P < 0.01) than all other treatment groups. The ADG of the A7P and A7E steers were not different (P > 0.05) from those of the control steers. The gain:feed ratio of the A7E steers was 41% higher (P < 0.01) than that of the V7P steers (Exp. 1). The results of Exp. 2 indicated that the control, ACDP, and V7P steers had greater (P < 0.01) ADG than all other treatment groups, but the gain:feed ratios were not different (P > 0.05) among all treatment groups. Lesion sizes differed by vaccine and injection site in both experiments. These data suggest that vaccinating beef steers s.c. in the ear produced gain:feed ratios and lesion size scores that were similar to prescapular vaccinations. However, more research is required to determine the immune response of vaccinating cattle in the ear.

Magnetic resonance lipid signals in rat brain after experimental stroke correlate with neutral lipid accumulation.

Proton magnetic resonance spectroscopy (MRS) signals from lipids in brain have been observed to increase after ischemic brain injury. However, neither the chemical identity nor the cellular location of these lipids has been established. The aim of the present study was to identify the origin of MRS lipid signals in rat brain after temporary (90 min) middle cerebral artery occlusion (MCAO). Fatty acyl proton signals were detected by short-echo one and two dimensional (1)H MRS in superfused brain slices from the infarcted hemisphere 1-5 days after MCAO. The intensities of these signals were strongly correlated with the amount of triacylglyceride and cholesterol ester in lipid extracts from the samples (r(2)=0.96, P<0.05) and were not correlated with the amount of free fatty acids in the tissue. Histological staining of tissue revealed the presence of neutral lipid droplets in infarcted regions. Dual labeling by immunohistochemistry demonstrated that these droplets were localized to microglia/macrophage (OX-42-labeled cells). These results strongly suggest that (1)H MRS lipid signals from brain after stroke arise from microglia/macrophage phagocytosis of cellular membranes.

MR spectroscopy study of dichloroacetate treatment after ischemic stroke.

In a double-blind, placebo-controlled study, we used 1H MR spectroscopy to assess the effect of a single infusion of sodium dichloroacetate on lesion lactate 1 to 5 days after ischemic stroke. Apparent trends toward a reduction in lactate/N-acetyl compound ratios were seen at the higher drug doses employed, and in patients treated in the first 2 days following infarction. Use of spectroscopic measures as endpoints is feasible in acute stroke clinical trials.

Autosomal dominant cerebral arteriopathy: neuropsychiatric syndrome in a family.

Though familial vascular leukoencephalopathy was described two decades ago, recent studies focus on a disorder termed Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a dominantly inherited disorder causing recurrent strokes and eventual dementia. The phenotypic boundaries of CADASIL remain indistinct and novel clinical features continue to arise in the literature. However, the associated histopathology is fairly consistent, typically demonstrating granular thickening of cerebral arterioles. The authors evaluated a 38-year-old man who suffered from progressive change in personality and intellect. His father, paternal aunt, and older sister had succumbed to a similar disorder. The authors examined relatives from three generations, including another sister with transient focal symptoms followed by persisting psychiatric disorder, and reviewed the radiographic studies from the propositus and his siblings. All the siblings showed diffuse white matter signal change on magnetic resonance imaging. Brain biopsy from the propositus revealed normal cortex and white matter but granular sclerosis of leptomeningeal arterioles. While the family's illness likely represents another instance of CADASIL, their presentation is unique because neuropsychiatric disorders predominate over focal ischemic symptoms.

Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain.

A novel approach is presented for imaging macromolecule and metabolite signals in brain by proton magnetic resonance spectroscopic imaging. The method differentiates between metabolites and macromolecules by T1 weighting using an inversion pulse followed by a variable inversion recovery time before localization and spectroscopic imaging. In healthy subjects, the major macromolecule resonances at 2.05 and 0.9 ppm were mapped at a nominal spatial resolution of 1 x 1 x 1.5 cm3 and were demonstrated to be highly reproducible between subjects. In subacute stroke patients, a highly elevated macromolecule resonance at 1.3 ppm was mapped to infarcted brain regions, suggesting potential applications for studying pathological conditions.

Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction.

BACKGROUND AND PURPOSE: We sought to determine whether lactate and N-acetyl signals measured by proton magnetic resonance spectroscopy (MRS) in the first days after stroke correlate with clinical measures of disability and functional outcome. METHODS: One-dimensional spectroscopic imaging was performed after stroke on 32 patients using a 2.1-T magnet. The Toronto Stroke Scale score at the time of the MRS study and the Barthel Index score at hospital discharge were determined from patient records. Lesion volume was estimated by a tracing algorithm from the scout magnetic resonance image obtained as part of the MRS study. The scaled lactate and N-acetyl signals from the voxel having the highest measured lactate were used to predict the clinical variables and lesion volume, as well as relative perfusion within the lesion, in those patients who underwent single-photon emission computed tomography (SPECT) blood flow imaging, using a multiple regression analysis. The correlation of lesion volume with the clinical variables was also evaluated. RESULTS: Lesion lactate signal was correlated with the Toronto Stroke Scale score, Barthel Index score, lesion volume, and SPECT score, all at P < .01. The N-acetyl level correlated with the Barthel Index score and lesion volume at P < .05. Lesion volume was also strongly correlated with the clinical variables (P < .0001). CONCLUSIONS: This is the first study to document the clinical predictive value of proton MRS measurements in patients after stroke. The association with functional outcome is stronger for lactate than for N-acetyl. Spectroscopic assessment of the metabolic status of cerebral tissues shortly after infarction may have significant clinical utility.

BOLD MRI monitoring of changes in cerebral perfusion induced by acetazolamide and hypercarbia in the rat.

To evaluate MRI methods for estimating cerebrovascular reserve, we computed changes in the R2* and R2 transverse relaxation rate and apparent diffusion coefficient (ADC) at 2.0 Tesla in five rats after administration of 30 mg of acetazolamide and in four rats during inhalation of 20% carbon dioxide gas. Significant decreases in R2*, corresponding to increases in gradient echo MRI signals, occurred in both the acetazolamide (average change -8.3%, P = 0.005) and the carbon dioxide (-2.7%, P = 0.009) treated animals. The computed values for R2 and ADC were unchanged. The magnitude of the gradient echo MRI changes observed should permit anatomic mapping of blood flow reactivity patterns in normal human subjects and in patients at risk for cerebrovascular disease.

Proton spectroscopy of human stroke: assessment of transverse relaxation times and partial volume effects in single volume steam MRS.

Proton T2 relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T2 values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T2 for lactate in patients was 780 +/- 257 ms, respectively (mean +/- SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T2, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.

Early temporal variation of cerebral metabolites after human stroke. A proton magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy has documented declines in normal metabolites and long-term elevation of lactate signal after stroke in humans. Within days of stroke, leukocytes infiltrating the infarct zone may produce much of the lactate seen in the subacute and chronic periods. METHODS: We examined 10 patients by localized proton magnetic resonance spectroscopy with one-dimensional spectroscopic imaging within the first 60 hours after acute nonhemorrhagic cerebral infarction, a period before abundant leukocyte infiltration. Follow-up studies on day 8 to 17 after stroke were performed on 7 of these patients. RESULTS: Initially, the lactate magnetic resonance signal was elevated in all patients. The N-acetyl-aspartate peak within the lesion was reduced below contralateral normal brain in all but two. At subsequent examination, significant declines had occurred in lesion maximum lactate and N-acetyl-aspartate signals, with average changes of -36 +/- 11% per week and -29 +/- 9% per week, respectively. Declines in lesion creatine/phosphocreatine and in choline-containing compound peaks occurred in some patients but did not attain statistical significance for the group as a whole. Estimated lesion volume correlated positively with both total (r = .75, P = .012) and lesion maximum (r = .74, P = .015) lactate signal. CONCLUSIONS: Elevated lactate signal is reliably detectable by magnetic resonance spectroscopy after acute cerebral infarction in humans. Clearance of lactate occurs despite the potential contribution of lactate-producing leukocytes in the subacute stage. Delayed loss of N-acetyl-aspartate signal in second examinations suggests that late death of viable cells may occur within the first 2 weeks after cerebral infarction.

Proton magnetic resonance spectroscopy in Creutzfeldt-Jakob disease.

We studied two patients with Creutzfeldt-Jakob disease by in vivo proton magnetic resonance spectroscopy and obtained spectra from an extract of biopsy tissue from a third patient. In vivo spectra from the two patients, 3 months and less than 1 month after symptom onset, revealed only minor changes. A second study of one of the patients 10 months after symptom onset found a decrease in N-acetylaspartate and other metabolites. Spectroscopy of the biopsy extract obtained 4 months after onset of symptoms showed no reduction in metabolites measured by in vivo spectroscopy, in accord with quantitative pathology showing no overall neuronal loss. Changes in metabolites detectable by proton magnetic resonance spectroscopy are not an early feature of this disease.

Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes.

Previous studies of human stroke by 1H nuclear magnetic resonance spectroscopy have shown elevation of lactate lasting 3 to 6 months. Complete metabolic turnover of the elevated lactate pool has been demonstrated 5 weeks after a stroke. Its cellular localization is among the first questions requiring clarification. Information pertinent to this question came to us from a patient with a 2-week-old stroke by 1H nuclear magnetic resonance spectroscopic imaging 1 week before his death led to neuropathologic examination of the brain. 1H spectra from voxels including the infarcts showed increased lactate and decreased N-acetylaspartate. Histopathology showed sheets of foamy macrophages in the infarct, but few neurons. Macrophage density ranged from 196 cells/mm2 near the surface of the infarct to 788 near its medial margin. Glial density was 500 to 800 cells/mm2. Lactate concentration in voxels including portions of the infarct was estimated at 7 to 14 mM. Voxels showing low N-acetylaspartate and high lactate on spectroscopic imaging were associated with histopathologic sections containing foamy macrophages. Brain macrophages--which begin to appear 3 days after infarction and gradually disappear over several months--could be a major source of elevated lactate signals that persist for months after stroke.

Proton magnetic resonance spectroscopy of cerebral lactate and other metabolites in stroke patients.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six. METHODS: One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec. RESULTS: All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. N-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in N-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct. CONCLUSIONS: Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future.

Localized proton NMR observation of [3-13C]lactate in stroke after [1-13C]glucose infusion.

To assess whether elevated lactate in stable stroke is being actively produced from blood glucose localized 1H NMR stimulated echo spectra were obtained from a patient in the region of a 32-day-old cortical infarct before and 60-100 min after infusion of [1-13C]glucose. Prior to the infusion the spectrum from the region of the infarct contained an elevated resonance from C3 lactate and a greatly reduced resonance from N-acetyl groups relative to an unaffected contralateral region. After the infusion two additional resonances were observed at 62 and -64 Hz relative to the unlabeled resonance of C3 lactate which were assigned on the basis of chemical shift and relative intensity to [3-13C]lactate. The [3-13C]lactate fractional enrichment in the infarct region was measured to be 32% which is within error one-half the average [1-13C]plasma glucose enrichment during the postinfusion NMR measurement. The result suggests that the stroke lactate pool was completely derived from infused glucose.

The relationship between radionuclide bone scans and dental examinations.

Bone scans were evaluated in 57 patients referred from the nuclear medicine clinic. Areas of normal and abnormal radiopharmaceutical accumulation in the maxilla and mandible were correlated with a clinical and radiographic dental examination. There was an 80% agreement between the areas of normal and abnormal uptake with the clinical and radiographic findings. This was statistically significant (p less than 0.001). Twenty-one patients had clinical and radiographic dental examinations that were within normal limits and yet had abnormal bone scans. Five of these 21 patients were subsequently seen on an emergency basis for treatment of dental abnormalities. These positive areas on the bone scans may be indicating areas of pathosis not detectable by conventional clinical and radiographic diagnostic techniques.

Femoral head osteonecrosis. Detection by magnetic resonance imaging versus single-photon emission computed tomography.

Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) examinations were compared for detection of femoral head osteonecrosis. Of 29 hips with clinical and roentgenographic evidence of osteonecrosis (18 histologically confirmed), 15 were Stage II, three transitional, six Stage III, and five Stage IV. MRI identified osteonecrosis in all 29 cases (100% sensitivity), and there were no false-positives (100% specificity). Of 24 osteonecrotic hips with technically adequate examinations, SPECT identified 14 (sensitivity 58%), and there were four false-positives (78% specificity). If Stages III and IV were eliminated, SPECT correctly identified ten of 15 (67% sensitivity).

Radioiodine treatment of Graves' disease. An assessment of its potential risks.

Concern about the side effects of radiation exposure has deterred physicians from using radioiodine treatment for Graves' disease, although the efficacy and safety of this treatment have been established in the 35 years since its introduction. In that time, no significant side effects have been discovered. We believe iodine-131 should be considered the treatment of choice in most patients with Graves' disease. This article reviews the current understanding of the risks in radioiodine treatment of Graves' disease, including the risks for teratogenicity, genetic damage, carcinogenesis, and cellular dysfunction.

Scintigraphic findings in a primary cerebral amyloidoma.

Bone, brain, and gallium scintigrams are presented of a 48-year-old man with biopsy-proven cerebral amyloidosis. Brain scintigraphy revealed a well-circumscribed accumulation of Tc-99m pertechnetate in the amyloidoma. Bone scintigraphy using Tc-99m methylenediphosphonate likewise exhibited increased activity in the same area. Gallium-67 citrate, however, failed to localize within the amyloidoma.

Scintigraphic detection of osteomyelitis with Tc-99m MDP and Ga-67 citrate: concise communication.

Using both Tc-99m methylene diphosphonate and gallium-67 citrate, images of the lower extremities in New Zealand white rabbits were obtained on sequential days after inoculation of tibias with Staphylococcus aureus. Gallium-67 scintigraphy was positive earlier in the course of infection than Tc-99m MDP scintigraphy. In addition to 4-hr Ga-67 scintigrams, 24-hr and 48-hr scintigrams were obtained, contributing substantially to interpretation. However, 72-hr Ga-67 scintigrams contributed little additional information.