Mechanisms underlying neuro-psychological sequelae of cranial RT remain to be elucidated. The purpose of this study was to examine the relationship between neuro-metabolites measured with MRS, RT dose, and neuro-psychological deficits. Twelve patients and 35 age/sex matched controls included. MRS at 1.5 T and cognitive assessment conducted at baseline and 6, 15, 27 months following RT and compared to data from 1 visit in controls. Neuro-psychological battery included: motor dexterity, visual attention/processing speed, visual working memory, visual perception, verbal learning, verbal working memory, single word vocabulary. Thalamus, caudate, putamen, hippocampus, temporal lobes and genu/splenium of corpus callosum contoured. Concentrations of N-acetylaspartate (NAA) and choline (Cho) in these regions expressed as ratios NAA/Cho and Cho/Cr (creatine). Linear mixed effects (LME) regression models examined associations among metabolite ratios, RT doses to contoured structures and performance on testing, and compared MRS findings for patients with controls. GLM was used for post-hoc analyses of individual time points. For patients: Male, n = 8. Primary site: infratentorial, n = 6; supratentorial, n = 5; leukemia, n = 1. Mean age at RT: 12 years (range, 8.6-16.1). Mean prescription: 50 Gy (range, 18-54). Overall LME analyses revealed no group differences in Cho/Cr but lower NAA/Cho in RT group based on region (p = 0.04). At individual time points, no group differences in regional NAA/Cho detected at baseline, but there was reduced NAA/Cho in splenium (p = 0.01) and thalamus (p = 0.038) 6 months following RT. For patients, a negative association between RT dose and NAA/Cho was detected (p = 0.014). Following RT, reduced NAA/Cho ratio in: temporal lobe predicted poorer verbal learning (p = 0.006) and visual perception (p = 0.049); caudate poorer motor dexterity (p = 0.028); genu poorer visual working memory (p = 0.03); and hippocampus poorer visual perception (trend p = 0.058). Increased mean dose to caudate associated with poorer verbal memory (p = 0.043); and genu with poorer verbal memory (p = 0.043) and visual attention/processing speed (p = 0.036). There were no other significant associations between RT dose to other structures and performance on testing. This prospective study suggests significant changes in NAA/Cho following cranial RT, and significant relationships between NAA/Cho, mean dose, and performance on neuro-psychological testing. Since NAA is considered a neuronal marker, our observations may suggest regional neuronal loss following RT with impairment in both neuronal integrity and function. Further evaluation of metabolites following RT may allow improved understanding of the mechanism of neuro-cognitive sequelae.

BACKGROUND AND PURPOSE: Neuroimaging methods have been used to improve our understanding of the topographic organization of the brain. In our study, proton 1H-MR spectroscopic imaging was used to evaluate frontal lobe function. The goal was to determine the relationship between neuropsychological measures of frontal lobe function and levels of a surrogate neuronal marker, N-acetylaspartate (NAA), in typically developing healthy children and adolescents. MATERIALS AND METHODS: Fifty-one healthy children (25 girls; 6.2–18.3 years of age; mean age, 12.3 ± 3.6 years) were examined. All children completed a neuropsychological assessment including measures of attention, executive function, memory, language, and visual and motor skills. 1H-MR spectroscopic imaging was performed by using a multisection spin-echo sequence at 1.5T. General linear model analysis of covariance was used to examine the relationship between the neuropsychological test scores and NAA/creatine (Cr) ratios, controlling for age and sex. RESULTS: A positive relationship between frontal lobe white matter NAA/Cr ratio and performance on 2 neuropsychological tests associated with frontal lobe function was detected. The Purdue Pegboard right-hand scores were higher with increasing NAA/Cr in the left frontal white matter (P = .047), and Stanford-Binet-IV "Bead Memory" scores improved with increasing NAA/Cr ratio in the right frontal white matter (P = .032). CONCLUSIONS: An association between frontal white matter NAA/Cr ratios and 1) measures of manual speed and dexterity, and 2) visual working memory was detected. Our data may provide a quantitative basis for assessment of frontal lobe impairments in disease states.

Background. Studies have confirmed the neuroprotective effect of diazoxide in canines undergoing hypothermic circulatory arrest ( HCA). A decreased N- acetyl- asparate: choline ( NAA: Cho) ratio is believed to reflect the severity of neurologic injury. We demonstrated that noninvasive measurement of NAA: Cho with magnetic resonance spectroscopy facilitates assessment of neuronal injury after HCA and allows for evaluation of neuroprotective strategies.Methods. Canines underwent 2 hours of HCA at 18 degrees C and were observed for 24 hours. Animals were divided into three groups ( n = 15 in each group): normal ( unoperated), HCA ( HCA only), and HCA + diazoxide ( pharmacologic treatment before HCA). The NAA: Cho ratios were obtained 24 hours after HCA by spectroscopy. Brains were immediately harvested for fresh tissue NAA quantification by mass spectrometry. Separate cohorts of HCA ( n = 16) and HCA + diazoxide ( n = 23) animals were kept alive for 72 hours for daily neurologic assessment.Results. Cortical NAA: Cho ratios were significantly decreased in HCA versus normal animals ( 1.01 +/- 0.29 versus 1.31 +/- 0.23; p = 0.004), consistent with severe neurologic injury. Diazoxide pretreatment limited neurologic injury versus HCA alone, reflected in a preserved NAA: Cho ratio ( 1.21 +/- 0.27 versus 1.01 +/- 0.29; p = 0.05). Data were substantiated with fresh tissue NAA extraction. A significant decrease in cortical NAA was observed in HCA versus normal ( 7.07 +/- 1.9 versus 8.54 +/- 2.1 mu mol/ g; p = 0.05), with maintenance of normal NAA levels after diazoxide pretreatment ( 9.49 +/- 1.1 versus 7.07 +/- 1.9 mu mol/ g; p = 0.0002). Clinical neurologic scores were significantly improved in the HCA + diazoxide group versus HCA at all time points.Conclusions. Neurologic injury remains a significant complication of cardiac surgery and is most severe after HCA. Magnetic resonance spectroscopy assessment of NAA: Cho ratios offers an early, noninvasive means of potentially evaluating neurologic injury and the effect of neuroprotective agents.

The site of lesion responsible for left hemispatial neglect after stroke has been intensely debated recently. Some studies provide evidence that right angular lesions are most likely to cause left neglect, whereas others indicate that right superior temporal lesions are most likely to cause neglect. We examine two potential accounts of the conflicting results: (1) neglect could result from cortical dysfunction beyond the structural lesion in some studies; and (2) different forms of neglect with separate neural correlates have been included in different proportions in separate studies. To evaluate these proposals, we studied 50 patients with acute right subcortical infarcts using tests of hemispatial neglect and magnetic resonance diffusion-weighted and perfusion-weighted imaging performed within 48 h of onset of symptoms. Left "allocentric" neglect (errors on the left sides of individual stimuli, regardless of location with respect to the viewer) was most strongly associated with hypoperfusion of right superior temporal gyrus (Fisher's exact test; p < 0.0001), whereas left "egocentric" neglect (errors on the left of the viewer) was most strongly associated with hypoperfusion of the right angular gyrus (p < 0.0001). Patients without cortical hypoperfusion showed no hemispatial neglect. Because the patients did not have cortical infarcts, our data show that neglect can be caused by hypoperfused dysfunctional tissue not detectable by structural magnetic resonance imaging. Moreover, different forms of neglect were associated with different sites of cortical hypoperfusion. Results help explain conflicting results in the literature and contribute to the understanding of spatial attention and representation in the human brain.

Background: Previous studies have indicated that focal brain damage can result in different types of "neglect dyslexia" (reading errors specific to the side of printed material contralateral to the side of brain damage).Aims: To identify the sites of lesions (or dysfunctional brain tissue) responsible for distinct types of neglect dyslexia, to inform a functional neuroanatomical model of brain regions involved in early stages of reading.Methods & Procedures: A battery of tests of hemispatial neglect and reading designed to distinguish neglect dyslexia in different reference frames (viewer-centred, stimulus-centred, and object-centred) was administered to 95 patients within 48 hours of onset of nondominant hemisphere stroke. Magnetic resonance diffusion and perfusion imaging was obtained on the same day as testing. Associations between each type of neglect dyslexia and areas of hypoperfusion and/or infarct were evaluated using chi-squared tests.Outcomes & Results: Viewer-centred neglect dyslexia was associated with hypoperfusion and/or infarct in right angular and supramarginal gyri and visual association cortex ("dorsal stream"). Stimulus-centred neglect dyslexia was associated with hypoperfusion and/or infarct of right superior temporal cortex ("ventral stream"). Object-centred neglect dyslexia was observed only with hypoperfusion and/or infarct of non-dominant superior temporal cortex in left-handed individuals.Conclusions: The identified associations provide evidence that different regions of cortex are critical for spatial attention to, or processing of, representations of words with distinct coordinate frames in the reading task.

Background: Adrenomyeloneuropathy (AMN) is the adult variant of X-linked adrenoleukodystrophy. The disease pathology is usually limited to spinal cord and peripheral nerves, and when this is the case, it is referred to as “pure” AMN. Histopathology shows cerebral involvement even in pure AMN; however, not much is known about the nature, extent, and clinical relevance of these findings. Objective: To investigate brain involvement in AMN patients with normal MRI, employing multislice MR spectroscopic imaging. Methods: Twelve men with pure AMN were compared with 19 age-matched healthy volunteers. Metabolite ratios (N-acetylaspartate [NAA]/choline [Cho], NAA/creatine [Cr], and Cho/Cr) were measured from seven brain regions. Global metabolite ratios were generated as an average of these seven regional ratios. The Expanded Disability Status Scale (EDSS) was used for neurologic evaluation. Results: The patients with AMN showed reduced global NAA/Cho (AMN 1.40 ± 0.16 vs controls 1.75 ± 0.34; p = 0.003)) and global NAA/Cr (AMN 2.32 ± 0.13 vs controls 2.62 ± 0.43; p = 0.03). Regionally, NAA/Cho was lowered in the internal capsule (AMN 1.30 ± 0.20 vs controls 1.69 ± 0.37; p = 0.002) and in parieto-occipital white matter (AMN 1.45 ± 0.19 vs controls 1.78 ± 0.55; p = 0.04). NAA/Cr was lowered in parieto-occipital white matter (AMN 2.34 ± 0.31 vs controls 2.83 ± 0.71; p = 0.04). EDSS demonstrated an inverse association with global NAA/Cr (r = −0.65, p = 0.02) and NAA/Cr in centrum semiovale (r = −0.73, p = 0.006) and in parieto-occipital white matter (r = −0.64, p = 0.02). Cho/Cr was not significantly elevated. Conclusions:1H-MR spectroscopic imaging is able to detect biochemical abnormalities suggestive of axonal damage even in the brains of patients with pure adrenomyeloneuropathy. The axonopathy is most prominent in internal capsule and parieto-occipital white matter and may contribute to clinical disability.

Activation of the left midfusiform gyrus in response to reading words and pseudowords is such a reliable finding in functional imaging that this region has been called "the visual word form area" (VWFA). However, this label has recently been challenged, because activation in VWFA is also observed in other lexical tasks. We evaluated whether VWFA is necessary, sufficient, or specialized for reading by examining how frequently acute lesions in VWFA disrupt tasks that require access to written word forms versus other lexical tasks. We administered lexical tasks with spoken and written input and output, and identified damage or dysfunction of VWFA and other regions of interest (ROI) on diffusion- and perfusion-weighted imaging (DWI and PWI) in 80 patients within 24 h of onset of acute left ischemic stroke. Associations between abnormalities in each region of interest and impairment on lexical tasks were evaluated with chi-squared tests. Damage or dysfunction of VWFA was not significantly associated with impairment of written word comprehension or lexical decision, but was significantly associated with impairment on all tasks requiring lexical output: oral reading and oral naming (visual or tactile input), and written naming. We account for these results and results from functional imaging by proposing that the left midfusiform gyrus normally has two roles in reading: (1) computation of location- and modality-independent grapheme sequences from written word stimuli, and (2) a modality-independent stage of lexical processing that links modality-specific input and output representations. VWFA is not necessary for the former because the right homologue of VWFA can immediately assume this role.

Normally, ventricular cerebrospinal fluid (CSF) contains low levels of all metabolite signals on proton magnetic resonance spectroscopic imaging (MRSI). We present here three cases (two with seizure disorders, one with a central nervous system lymphoma) who presented with unusually elevated CSF signals on MRSI. Based on chemical shifts and in vitro studies (in one case), the signals were assigned to propan-1,2-diol (PD), acetone, and lactate, respectively. These compounds were either exclusively, or more readily, detected in CSF than in brain. Proton MRSI conveniently screens both brain and CSF for abnormal metabolism simultaneously.

Magnetic resonance (MR) imaging is a useful tool to study the anatomy of the testis while 31P magnetic resonance spectroscopy (MRS) provides a non-invasive alternative method to demonstrate the metabolic status of testes. This study was designed to test whether the protective role of cyclosporine in experimental unilateral blunt testicular trauma (UBTT) could be assessed by 31P MRS. Male Wistar rats (n=30) aged 20 days were randomised into group I (sham surgery), group II (UBTT) and group III (UBTT and cyclosporine for 7 days). Contralateral testicles of 5 rats from each group was evaluated by 31P MRS at 30 and 60 days of age and phosphomonoesters (PM), phosphodiesters (PD), and adenosine triphosphate (ATP) levels were measured. At 60 days of age the PM/ATP ratio was 0.32±0.08 in group I whereas it was 0.68±0.31 in the group II (p<0.05). Group III rats showed PM, PD and PM/ATP ratios similar to the controls. In conclusion, it is observed that UBTT causes contralateral testicular damage which could be prevented by short-term cyclosporine treatment and 31P MRS is an excellent modality for such an evaluation.

OBJECTIVES:To prognosticate and assess the metabolic status of germ cells of the testis after unilateral blunt testicular trauma using both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). MRI is a noninvasive technique suitable for evaluating testicular trauma, and MRS is useful in assessing the metabolic status of the testis.METHODS:The right testis of 35 male prepubertal Wistar rats, aged 30 days, was explored through an inguinal incision. The rats were randomized into control (group 1, sham surgery, n = 10) and study (n = 25) groups. The study group received unilateral blunt testicular trauma to the right testis. T(1)- and T(2)-weighted proton MRI of the ipsilateral testis were taken 6 hours after sham surgery or injury, and the rats were stratified on the basis of the absence or presence of intratesticular hemorrhage on MRI into groups 2 (n = 14) and 3 (n = 11), respectively. At 60 days of age, the contralateral testis of each rat was evaluated by 31P MRS and histologic examination. Quantification of phosphomonoesters, phosphodiesters, phosphocreatine, and adenosine triphosphate (gamma, alpha, and beta) was done.RESULTS:A statistically significant difference (P <0.05) in the phosphomonoester/adenosine triphosphate ratio, seminiferous tubular diameter, and Johnsen score of the contralateral testis was observed, indicating decreased testicular maturation of the contralateral testis in group 3 rats compared with groups 1 and 2.CONCLUSIONS:MRI after testicular trauma helped to stratify the extent of injury as determined by the presence or absence of intratesticular hemorrhage with prognostic value; 31P MRS and histologic examination revealed that testicular trauma significantly affects the maturation of the contralateral testis.

OBJECTIVES:The effect of unilateral blunt testicular trauma on subsequent testicular function is still debated. None of the experimental studies had the exact grading of testicular injury and evaluation of hormone status and hence this study was designed. METHODS:Twenty male prepubertal (20 days old) Wistar rats were divided into two groups: group 1 (n = 10) underwent sham surgery; group 2 (n = 10) underwent blunt trauma to the right testis by a 5-g sterile weight dropped three times on the testis from a height of 10 cm. T(1)-weighted and T(2)-weighted magnetic resonance images were taken within 6 hours to confirm grade I injury. At 60 days of age, blood samples were obtained from each rat for follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels, and both testes of each rat were harvested separately for DNA flow cytometric analysis. RESULTS:Group 2 rats had significantly reduced (P <0.001) haploid cell populations in both right and left testis compared with the corresponding testis of the group 1 rats. Within group 2, the right testis was significantly (P <0.001) more affected. Serum levels of testosterone were significantly lower (P <0.05) and follicle-stimulating hormone (P <0.01) and estradiol (P <0.05) levels were significantly higher in group 2 rats than in group 1 rats. However, the luteinizing hormone levels were not significantly different. CONCLUSIONS:Grade I unilateral blunt testicular trauma in prepubertal rats significantly affected germ cell maturation in both ipsilateral and contralateral testis and altered the sex hormone profile.

For the assessment of germ-cell maturation of the seminiferous tubules, DNA flowcytometry is a rapid and sensitive method. Phosporus 31P magnetic resonance spectroscopy (MRS) is a non-invasive alternative that demonstrates the metabolic status of the testis, reflecting the type and relative proportion of germ cells in the testis. This study was designed to evaluate the utility of 31P MRS in reflecting the haploid-cell population of the testis as measured by DNA flowcytometry. A single testicle was evaluated in male Wistar pre-pubertal rats at 30, 40, 50, and 60 days of age. In order to minimize the contamination of signals from the contralateral testis, scrotum, and tail, the technique was modified and the testis was evaluated ex-vivo with an intact blood supply. At 30 days of age the percentage of haploid cells was 43.6 ± 1.8, and this increased to 72.7 ± 1.4 at 60 days of age. During this period, the testicular phosphomonoester/adenosine triphosphate (PM/ATP) ratio changed from 1.70 ± 0.21 to 0.32 ± 0.08. There was a significant (P < 0.001) linear correlation between the proportion of haploid cells evaluated by DNA flowcytometry and the PM/ATP ratio evaluated by 31P MRS. 31P MRS is thus a reliable, noninvasive technique for accurately assessing the status of the seminiferous epithelium.

Metabolite mapping of human filarial parasite, Brugia malayi was carried out in vitro as well as in situ in host Mastomys coucha by 31P nuclear magnetic resonance (NMR) spectroscopy. Detection of parasites by visualizing contrast spots due to pathologic changes was observed by 1H magnetic resonance imaging (MRI). Major metabolites of adult B. malayi observed by 31P-NMR spectroscopy were of sugar phosphates (SP), phosphomonoesters (PME), glycerophosphoryl-ethanolamine (GPE), -choline (GPC), phosphoenolpyruvate (PEP), inorganic phosphate (Pi), nucleoside diphosphosugar and nucleotides-mono, -di and -tri phosphates. PEP and GPC were present in high concentration; PEP being the major energy reservoir and GPC the major phospholipid in this species of filaria. The 31P NMR spectra of testis of mastomys, showed seven major peaks of SP, PME, phosphocreatine (PCr), phosphodiesters (PDE), Pi, and nucleotides di- and tri-phosphates. The 31P-NMR spectra of testis of B. malayi infected animal also consisted of seven major peaks with significant decrease in the SP and PME peak showing changes in the carbohydrate and lipid metabolism of filaria infected testis. Thus, in vivo 31P MRS provided a non-invasive assessment of tissue bioenergetics and phospholipid metabolism.