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.

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.

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.

Failure of Gallium-67 scintigraphy to identify reliably noninfectious interstitial nephritis: concise communication.

Gallium-67 scintigraphy has been reported to be useful in the diagnosis of noninfectious interstitial nephritis. We studied 12 patients with Ga-67 citrate that were diagnosed as having noninfectious interstitial nephritis on renal biopsy. Only seven of the twelve patients with interstitial nephritis on biopsy were scan-positive. Gallium-67 scintigraphy may not reliably identify noninfectious interstitial nephritis.

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.

Predicting the cure of osteomyelitis under treatment: concise communication.

The right tibias of sixty-six rabbits were injected with a suspension of Staphylococcus aureus and sodium morrhuate. After four weeks, 43 rabbits developed osteomyelitis and were started on a course of antibiotics. During treatment a gallium-67 scintigram was obtained every two weeks, for up to 10 weeks. During the treatment weeks, 25 rabbits developed negative gallium-67 scintigrams and were killed. All 25 had negative bacteriologic cultures of the right tibia. At the end of 10 wk after start of treatment, the 18 rabbits with persistently positive scintigrams were killed. Eleven of these had positive bacteriologic cultures of the tibia, and seven were negative. The findings suggest that sequential gallium-67 scintigrams may be useful in predicting the cure of osteomyelitis during treatment.

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.

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.

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.

The role of Tc-99m MDP and Ga-67 citrate in predicting the cure of osteomyelitis.

Twenty rabbits with chronic osteomyelitis of the tibia were treated for eight weeks and then scanned with Tc-99m MDP and Ga-67 citrate. All were sacrificed and bacteriologic cultures of the tibia were obtained. All rabbits had positive Tc-99m MDP scans at the end of treatment despite thirteen cures of osteomyelitis. Eight had negative gallium scans and negative cultures. Five of the twelve positive gallium scans had negative cultures, while seven had positive cultures. Tc-99m MDP alone is not sensitive enough to be useful in predicting the cure of osteomyelitis, and combining Tc-99m MDP and Ga-67 citrate scintigrams offers no additional information over the Ga-67 citrate scintigram alone in follow-up of osteomyelitis.

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.

Angiographic and scintigraphic findings in fibrosing mediastinitis.

The clinical and morphologic findings in the case of a 47-year-old man with fibrosing mediastinitis, most probably due to histoplasmosis, are described. Radionuclide angiography demonstrated obstruction of the superior vena cava with collateral vascularization. Computed tomography demonstrated a large calcific mass interposed between the pulmonary artery and superior vena cava suggesting potential pulmonary vasculature involvement. For this reason, pulmonary scintigraphy was performed which showed right lung perfusion and ventilation defects. Radionuclide angiography and pulmonary scintigraphy complement each other in determining the extent of vascular involvement with fibrosing mediastinitis. However, contrast venography is necessary to correctly delineate the anatomy of the obstructed superior vena cava and its collaterals.

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.

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).

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.