Quantitative cerebral blood flow in dynamic susceptibility contrast MRI using total cerebral flow from phase contrast magnetic resonance angiography.

Dynamic susceptibility contrast magnetic resonance imaging during bolus injection of gadolinium contrast agent is commonly used to investigate cerebral hemodynamics. The large majority of clinical applications of dynamic susceptibility contrast magnetic resonance imaging to date have reported relative cerebral blood flow values because of dependence of the result on the accuracy of determining the arterial input function, the robustness of the singular value decomposition algorithm, and others. We propose a calibration approach that directly measures the total (i.e., whole brain) cerebral blood flow in individual subjects using phase contrast magnetic resonance angiography. The method was applied to data from 11 patients with intracranial pathology. The sum of squares variance about the mean (uncorrected: white matter = 105.6, gray matter = 472.2; corrected: white matter = 34.1, gray matter = 99.8) after correction was significantly lower for white matter (P = 0.045) and for gray matter (P = 0.011). However, the mean gray and white matter cerebral blood flow in the contralateral hemisphere were not significantly altered by the correction. The proposed phase contrast magnetic resonance angiography calibration technique appears to be one of the most direct correction schemes available for dynamic susceptibility contrast magnetic resonance imaging cerebral blood flow values and can be performed rapidly, requiring only a few minutes of additional scan time.

Exploring the relationship of macrophage colony-stimulating factor levels on neuroaxonal metabolism and cognition during chronic human immunodeficiency virus infection.

Macrophage colony-stimulating factor (M-CSF) promotes macrophage differentiation, increases susceptibility of macrophages to viral infection, and enhances human immunodeficiency virus (HIV) replication in infected macrophages. Given the current model of HIV neuropathogenesis, which involves monocyte trafficking into the central nervous system, immune factors linked with macrophage maturation and survival may be associated with cognitive decline (measured by neuropsychological z-score [NPZ-8] or Memorial Sloan-Kettering [MSK] score) and alterations in a marker of neuronal integrity, N-acetylaspartate (NAA). Fifty-four chronically infected HIV+ subjects underwent neuropsychological assessment, magnetic resonance spectroscopic imaging, and quantification of M-CSF in plasma and cerebrospinal fluid (CSF) at baseline. Thirty-nine of those subjects underwent further examination at 3 and 10 months after initiation of combination antiretroviral therapy (ART) regimens. Within 3 months of therapy use, CSF M-CSF and viral RNA levels were reduced, whereas NAA concentrations in many brain regions were increased. Neither baseline levels nor the change in M-CSF levels had the ability to predict changes in NAA levels observed after 10 months of combination ART use. At study entry those with the lowest M-CSF levels in the CSF had the least cognitive impairment (NPZ-8). Those who had higher baseline CSF M-CSF levels and exhibited larger decreases in M-CSF after therapy, tended to have greater cognitive improvement after 10 months. Increased prevalence of M-CSF in the setting of HIV infection could contribute to neuronal injury and may be predictive of cognitive impairment.

Diffusion tensor imaging in children and adolescents: reproducibility, hemispheric, and age-related differences.

UNLABELLED: We evaluated intra-rater, inter-rater, and between-scan reproducibility, hemispheric differences, and the effect of age on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in healthy children (age range 5.5-19.1 years) examined with a clinical diffusion tensor imaging (DTI) protocol at 1.5 T, using a region of interest (ROI) methodology. Measures of reliability and precision were assessed in six ROIs using two different ROI shapes (polygonal and ellipsoidal). RESULTS: Highly reproducible values of ADC and FA were obtained with the polygonal method on intra-rater (coefficients of variation

Evidence for cortical dysfunction and widespread manganese accumulation in the nonhuman primate brain following chronic manganese exposure: a 1H-MRS and MRI study.

Exposure to high levels of manganese (Mn) is known to produce a complex neurological syndrome with psychiatric disturbances, cognitive impairment, and parkinsonian features. However, the neurobiological basis of chronic low-level Mn exposure is not well defined. We now provide evidence that exposure to levels of Mn that results in blood Mn concentrations in the upper range of environmental and occupational exposures and in certain medical conditions produces widespread Mn accumulation in the nonhuman primate brain as visualized by T1-weighted magnetic resonance imaging. Analysis of regional brain Mn distribution using a "pallidal index equivalent" indicates that this approach is not sensitive to changing levels of brain Mn measured in postmortem tissue. Evaluation of longitudinal 1H-magnetic resonance spectroscopy data revealed a significant decrease (p = 0.028) in the N-acetylaspartate (NAA)/creatine (Cr) ratio in the parietal cortex and a near significant decrease (p = 0.055) in frontal white matter (WM) at the end of the Mn exposure period relative to baseline. Choline/Cr or myo-Inositol/Cr ratios did not change at any time during Mn exposure. This indicates that the changes in the NAA/Cr ratio in the parietal cortex are not due to changes in Cr but in NAA levels. In summary, these findings suggest that during chronic Mn exposure a significant amount of the metal accumulates not only in the basal ganglia but also in WM and in cortical structures where it is likely to produce toxic effects. This is supported by a significantly decreased, in the parietal cortex, NAA/Cr ratio suggestive of ongoing neuronal degeneration or dysfunction.

Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury.

BACKGROUND: Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function. METHODS AND FINDINGS: We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6-16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared. Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03). CONCLUSIONS: Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.

Noninvasive assessment of brain injury in a canine model of hypothermic circulatory arrest using magnetic resonance spectroscopy.

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 micromol/g; p = 0.05), with maintenance of normal NAA levels after diazoxide pretreatment (9.49 +/- 1.1 versus 7.07 +/- 1.9 micromol/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.

Quantitative proton magnetic resonance spectroscopic imaging: regional variations in the corpus callosum and cortical gray matter.

PURPOSE: To evaluate regional variations of metabolite concentrations in normal adult brain cortical gray matter regions, and the genu and splenium of the corpus callosum, using proton magnetic resonance spectroscopic imaging (MRSI). MATERIALS AND METHODS: Quantitative, multislice proton MRSI (TR/TE = 2000/280 msec) was performed in 12 normal human volunteers (age = 39 +/- 6 years, 7 male). Metabolite concentrations in selected cortical gray matter regions and the corpus callosum were estimated using the phantom replacement methodology. RESULTS: Frontal and parietal gray matter (PGM) showed strong differences in choline-containing compound (Cho) concentrations; in particular, Cho was higher in mesial frontal gray matter than in both dorsolateral prefrontal cortex (P < 0.0005) and PGM (P < 0.004). In contrast, both N-acetylaspartate (NAA) and creatine (Cr) were relatively uniformly distributed in the cortical gray matter regions evaluated. Significant metabolic differences were found between the genu and splenium of the corpus callosum. Cho concentrations were significantly higher in genu than splenium (P < 0.005), while Cr was lower (P < 0.004). NAA showed a trend to be higher in the splenium than the genu (P = 0.05). CONCLUSION: Metabolite concentrations, particularly Cho, showed strong regional variations both within cortical gray matter regions and between the genu and splenium of the corpus callosum. Mesial frontal regions showed the highest Cho signals. Differences in spectra presumably reflect underlying changes in structure and cellular composition. Normal spectral variations should always be considered when evaluating pathology within those brain regions.

Determination of relaxation characteristics during preacute stage of lysophosphatidyl choline-induced demyelinating lesion in rat brain: an animal model of multiple sclerosis.

Relaxation time measurements were carried out during the preacute stage of lesion progression in an animal model of demyelination created in the internal capsule (ic) area of the rat brain using lysophosphatidyl choline (LPC). T1 and T2 were determined both before and after 36 h of lesion creation. Histology carried out on the rats after MR measurements showed focal demyelinating lesion and surrounding edema with prominent infiltration of inflammatory cells. Both T1 and T2 were statistically higher for the lesion compared to that determined before lesion creation. Percentage increase in T2 was found to be higher by approximately 45% compared to before lesion creation while T1 showed about 25% increase. Increase in T1 and T2 may be attributed to the early acute inflammatory response due to LPC. The beginning of the inflammatory response following LPC injection may also be a contributing factor. The study demonstrates that the quantitative estimate of MR relaxation provides useful information on the pathological events occurring during the early phase of the progression of demyelination.

Anatomy of spatial attention: insights from perfusion imaging and hemispatial neglect in acute stroke.

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.

The roles of the "visual word form area" in reading.

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.

Metabolites in ventricular cerebrospinal fluid detected by proton magnetic resonance spectroscopic imaging.

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.

Evaluation of skin tumors by magnetic resonance imaging.

In vivo magnetic resonance imaging (MRI) is a powerful noninvasive technique in medical diagnosis; however, its application to analyze skin disorders is still at initial stages. To check whether MRI can be used as a noninvasive tool to analyze skin tumors, we carried out MRI of mice after treatment with benzo[a]pyrene (BP), a well known carcinogen. MRI was done on whole mice and was particularly focused on various layers and regions of interest of the skin: dermis, epidermis, and tumor. Initial MRIs of mice bearing skin tumors of 4, 8, 12, and 16 weeks after inducing BP clearly revealed the appearance of tumor. The MRIs of tumor-bearing mice with 20-week-old tumor development showed invasion to adjacent internal anatomic structures. The MRI data were in good agreement with the extent of cellular atypia and neoplastic changes that are typical of squamous cell carcinoma as noticed from the histopathologic findings. Therefore, MRI seems to have the potential to evaluate the tumor invasions equally well as that of histopathology or other clinical findings.

Protective role of cyclosporine in experimental unilateral blunt testicular trauma: evaluation by 31P MR spectroscopy.

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.

Sequential diffusion-weighted magnetic resonance imaging study of lysophosphatidyl choline-induced experimental demyelinating lesion: an animal model of multiple sclerosis.

PURPOSE: To differentiate the surrounding edema from the focal demyelinating lesion during the early phase of the lesion using an apparent diffusion coefficient (ADC), and to monitor the changes in ADCs during the complete progression of a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion, an animal model of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen rats divided into two groups-demyelinating lesion (group I, N = 12) and vehicle group (saline injected; group II, N = 6)-were studied. A 0.2-microl quantity of 1% LPC solution in isotonic saline was injected in the rat brain internal capsule (IC) area to create the demyelinating lesion. Six rats were used exclusively for histology. Diffusion-weighted (DW) images were acquired at different diffusion weightings on the 3rd, 5th, 10th, 15th, and 20th days after LPC injection. ADC was measured from three regions of interest (ROIs) within the IC: focal demyelinating lesion (area A), surrounding area of the lesion (area B), and contralateral IC area (area C). RESULTS: Histology revealed demyelination of the IC area during the early phase of lesion progression up to day 10 and remyelination thereafter. Elevated ADCs were observed for the surrounding edematous area (area B), compared to the focal demyelinating lesion (area A) during the early phase of the demyelination process, while substantial reduction of ADCs was noticed during remyelination for both regions. CONCLUSION: Measurement of ADC showed clear differentiation of the surrounding edema from the LPC-induced focal demyelinating lesion in rats, especially during the early phase of the lesion progression.