Dawn E. Saunders

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy

Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short‐ (30 ms) and long‐ (136 ms) echo time (TE) 1H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo‐Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high‐grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and δ1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade. Magn Reson Med 49:223–232, 2003.

Continuing Ischemic Damage After Acute Middle Cerebral Artery Infarction in Humans Demonstrated by Short-Echo Proton Spectroscopy

BACKGROUND AND PURPOSEnProton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction.nnnMETHODSnDiagnostic MRI and short-echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months.nnnRESULTSnSignificant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N-Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N-acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period.nnnCONCLUSIONSnThe demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

Measurement of Infarct Size Using MRI Predicts Prognosis in Middle Cerebral Artery Infarction

BACKGROUND AND PURPOSEnAn accurate measure of the severity of ischemic insult and the resulting prognosis is needed to assess the effectiveness of new treatments for acute stroke. We studied the reproducibility and accuracy of measurements of infarct volume with MRI and correlated the measurements with outcome.nnnMETHODSnInfarct volume was measured on T2-weighted images with the Analyze image analysis software. This technique was found to be highly accurate and reproducible.nnnRESULTSnMeasurements of infarct volume were found to be highly accurate and reproducible. Twenty-one patients (mean age, 66.5 years; range, 28 to 90 years) with cortical middle cerebral artery territory infarcts in whom adequate data could be obtained were studied within 72 hours from onset (mean delay to MRI, 27.5 hours; range, 5 to 72 hours). The Scandinavian Stroke Scale was used to calculate a prognostic score, and clinical outcome was assessed at 3 months. Infarct volume was found to significantly predict outcome. Mean infarct volume in the independent patients was 35.7 +/- 29.7 cm3 compared with 88.3 +/- 71.3 cm3 in dependent patients and 166.5 +/- 65.9 cm3 in dead patients (F = 10.52, P < .001). Patients with an initial infarct volume less than 80 cm3 were found to have a better outcome than those with larger infarct volumes. Secondary hemorrhage visible on MRI also predicted a poor outcome. In contrast, the Scandinavian Stroke Scale did not significantly predict outcome.nnnCONCLUSIONSnThe results demonstrate that measurement of the size of middle cerebral artery infarction with MRI is a useful tool in assessing prognosis and will have a valuable role in assessing new therapeutic agents.

Aging of the adult human brain: In vivo quantitation of metabolite content with proton magnetic resonance spectroscopy

The purpose of this study was to examine the effect of aging on brain metabolite concentrations, including N‐acetyl aspartate (NAA), the major marker of neurones, using short echo proton spectroscopy. Single‐voxel proton spectra (TE 30 msec, TR 2 seconds) were obtained from white and gray matter using automated software (PROBE, G.E., Milwaukee, WI). Spectra were analyzed using the variable projection technique. Thirty healthy volunteers were studied within the age range 24–89 years. No significant trend in change of concentrations of NAA, total creatine, total choline or myo‐inositol were seen with age. The total creatine concentration of parietal white matter in the over 60 age group (6.5 ± 0.3 mmol/l) was significantly higher than the under 60 age group (6.0 ± 0.4 mmol/l; P < 0.05). No other significant difference between the two age groups was seen. The tissue concentration of the major neuronal marker, NAA, does not decline with age. No age‐related changes in the concentrations of choline and myo‐inositol and occipital gray matter total creatine were observed. These results provide a normal range of values for spectroscopically detectable metabolites within the regions studied, against which neurological diseases such as Alzheimers disease can be compared in vivo. J. Magn. Reson. Imaging 1999;9:711–716.

MR spectroscopy in stroke

Magnetic resonance spectroscopy (MRS) is a non-invasive in vivo method that allows the investigation of biochemical changes in both animals and humans. The application of MRS to the study of stroke has made possible dynamic studies of intracellular metabolism of cerebral ischaemia. The majority of the stroke studies have been carried out using proton [1H]-MRS which allows the detection of N-acetyl aspartate (NAA), a neuronal marker. [1H]-MRS changes in humans demonstrate that after an infarct, lactate appears, while NAA and total creatine are reduced compared to the contralateral hemisphere. Longitudinal studies demonstrate a further reduction of NAA suggesting that ischaemic injury continues for more than a week following infarction. Major advances in the treatment of acute stroke require the accurate prediction of the mortality of stroke patients. Patients with large infarcts are known to do badly. In patients with small infarcts, less than 80 cm3, the addition of core NAA concentrations and cerebral blood flow have enabled the identification of some of the patients likely to benefit from new drug treatment.

Measurement of Initial N-Acetyl Aspartate Concentration by Magnetic Resonance Spectroscopy and Initial Infarct Volume by MRI Predicts Outcome in Patients With Middle Cerebral Artery Territory Infarction

BACKGROUND AND PURPOSEn(1)H MR spectroscopy can be used to study biochemical changes occurring in the brain in stroke. We used it to examine the relationship between metabolite concentration (N-acetyl aspartate [NAA], lactate, cholines and creatines), size of infarct, clinical deficit, and 3-month clinical outcome in patients with middle cerebral artery (MCA) territory infarction.nnnMETHODSnThirty-one patients with acute MCA territory infarction were recruited within 72 hours of the onset of symptoms. Single-voxel short echo time stimulated echo acquistion mode spectroscopy was used to obtain metabolite data from the infarct core. Metabolite concentrations were determined with use of variable projection time domain-fitting analysis. Infarct size was determined with T2-weighted images. Patient outcome groups at 3 months were independent, dependent, or dead.nnnRESULTSnAll patients (100%; 95% CI 75% to 100%) who had an infarct >70 mL did poorly. Eighteen of 20 patients (90%; 95% CI 68% to 99%) with a core NAA concentration <7 mmol/L did poorly at 3 months, whereas 7 of 11 patients (64%; 95% CI 31% to 89%) with an initial NAA concentration >7 mmol/L did well. Combining these results showed that all patients who had an initial infarct volume >70 mL did poorly, irrespective of the NAA concentration. Of those patients with infarcts <70 mL, those who had a core NAA concentration >7 mmol/L did well (88%; 95% CI 47% to 100%), whereas those with a lower NAA concentration did poorly (80%; 95% CI 44% to 97%). There was no association between other metabolite concentrations and outcome.nnnCONCLUSIONSnInfarct volume and NAA concentration can together predict clinical outcome in MCA infarction in humans.

Magnetic resonance neurography of the median nerve

A magnetic resonance imaging sequence, combining fat and flow suppression with T2 weighting, has been used to produce high conspicuity images of the median nerve within the carpal tunnel. Standard maximum intensity projection techniques were then used to produce three-dimensional (3D) reconstructions of the nerve. Comparison of 3D projections with the wrist in a neutral position and wrist flexed at 45 degrees depicted changes in the shape and course of the median nerve through the carpal tunnel of normal volunteers. In some cases of carpal tunnel syndrome evidence of a localized compression was observed. A 3D image of a nerve may help in the diagnosis of peripheral neuropathy and be an aid to surgery of or near major nerves.

Characteristics of Childhood Arterial Ischemic Stroke With Normal MR Angiography

Background and Purpose— The purposes of this study were to describe clinical and radiological characteristics of children with arterial ischemic stroke and normal MRA to compare them with children with arterial ischemic stroke and abnormal MRA. Methods— We conducted a retrospective review of clinical records and imaging. Results— Forty children with arterial ischemic stroke and normal MRA were identified (24 male; median age, 55 months). MRA had been acquired <24 hours of symptom onset in 4, at 24 to 48 hours in 10, 48 to 96 hours in 10, 4 to 7 days in 10, and >1 week in 6 children (median, 4 days). Ten of 40 had prior diagnoses (5 cardiac, 5 malignancies). Other risk factors were identified in 30 (1 in 17 and >1 in 13; prothrombotic abnormalities in 14, prior Varicella in 7, anemia in 7, minor trauma in 4). Infarction was confined to the lenticulostriate branches of the middle cerebral artery in 21 of 40. Two patients had further clinical events, both with new infarcts; 28 patients were reimaged and MRA remained normal in all. Although similar in terms of age and gender to those with abnormal MRA, children with normal MRA were significantly more likely to have at least 1 RF (P=0.012). Those with abnormal MRA were significantly more likely to have multiple territory infarcts (P<0.001), but lesion topography was otherwise not predictive of abnormal MRA (P=0.45). Abnormal MRA was significantly associated with clinical recurrence (P<0.001). Conclusions— Children with arterial ischemic stroke and normal MRA are not a distinct demographic group but are more likely to have single-territory lesions and have nonvascular risk factors. The stroke mechanism in children with normal MRA remains unclear.

Monobloc and bipartition in craniofacial surgery.

Background The frontofacial monobloc advancement with osteogenic distraction is increasingly used as a surgical treatment for children with complex craniosynostosis-associated syndromes. However, the subfrontal osteotomy cuts to free the facial skeleton from the skull base require extradural retraction of the frontal lobes. The purpose of this study was to determine the frequency and degree of radiologically identifiable frontal lobe changes and whether any such changes affected the patients’ outcome. Methods The clinical records and preoperative and postoperative computed tomography imaging of all patients undergoing monobloc frontofacial distraction advancement (with or without bipartition) were reviewed. A retrospective medical notes review was undertaken to assess any patient or surgically related factors that might predispose to frontal lobe changes and evaluate outcome from surgery. Where available, magnetic resonance imaging scans were reviewed to compare outcome with that on computed tomography. Results Fifty cases were identified as suitable for the study. Eighteen patients (36%) had no frontal lobe changes. Thirty-two cases (64%) did have changes that appeared related to the position of maximum retraction during subfrontal osteotomy cuts. There were no changes in the incidence/extent of these changes over time or of any link to the patients’ diagnosis, age at surgery, phenotype severity, surgery type, or any surgical or postoperative adverse events. We found no evidence that these changes were responsible for neurologic problems (eg, epilepsy) or reduced cognitive function. Conclusions This study reveals a high incidence of frontal lobe changes demonstrable on neuroimaging following the frontofacial monobloc procedure reflecting the retraction points during surgery. Although no postoperative disability was reported, it is clearly important to consider more detailed neuropsychologic testing and review current surgical techniques to ensure that such changes are kept to a minimum.