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Biomedical subjects

Peter B Barker

Publications and source records attributed to Peter B Barker.

At least 19 recordsLinked to original sources

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<or=2.7%) and inter-rater (coefficients of variation<or=4.8%) reproducibility. For between-scan reproducibility, the coefficients of variation were <or=5.0%. Mean asymmetry indices were in the range from -4% to 9% for FA and from -6% to 3% for ADC. ADC showed significant negative correlation with age in 13 of 15 examined fiber tracts and FA increased significantly in three fiber tracts. Our results show that the evaluated DTI protocol is suitable for clinical application in pediatric population.

Adolescent↗

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.

Animals↗

Restoring cerebral blood flow reveals neural regions critical for naming.

We identified areas of the brain that are critical for naming pictures of objects, using a new methodology for testing which components of a network of brain regions are essential for that task. We identified areas of hypoperfusion and structural damage with magnetic resonance perfusion- and diffusion-weighted imaging immediately after stroke in 87 individuals with impaired picture naming. These individuals were reimaged after 3-5 d, after a subset of patients underwent intervention to restore normal blood flow, to determine areas of the brain that had reperfused. We identified brain regions in which reperfusion was associated with improvement in picture naming. Restored blood flow to left posterior middle temporal/fusiform gyrus, Broca's area, and/or Wernicke's area accounted for most acute improvement after stroke. Results show that identifying areas of reperfusion that are associated with acute improvement of a function can reveal the brain regions essential for that function.

Aphasia, Broca↗

MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome.

OBJECTIVE: Cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and autopsy studies have suggested that brain iron may be reduced in restless legs syndrome (RLS). Further analysis of the data also suggests that diminished brain iron may selectively be for early-onset RLS. This study was designed to replicate and extend our previous findings, specifically with regard to early-onset RLS. In this study our primary hypothesis was that substantia nigra (SN) iron index would be decreased in early-onset RLS compared to controls. METHODS: The iron concentration or 'iron index' in 10 brain regions was determined using MRI in 39 controls and in 22 early-onset and 19 late-onset RLS subjects. The Johns Hopkins RLS severity (JHRLSS) scale was used to define disease severity. RESULTS: The mean iron index from the SN was significantly lower in the early-onset RLS compared to controls (t=2.5, P=0.016), while late-onset RLS and controls did not differ. There was a significant negative Spearman rank correlation between SN iron index and JHRLSS scale for the control-early-onset-RLS cohort (rho=-0.32, P=0.016). CONCLUSIONS: The current MRI results in combination with previous autopsy data support the role of low brain iron in the SN in at least those with early-onset RLS symptoms.

Age of Onset↗

Musculoskeletal tumors: use of proton MR spectroscopic imaging for characterization.

PURPOSE: To determine the value of multivoxel proton magnetic resonance spectroscopic imaging (MRSI) in distinguishing malignant skeletal tumors from benign tumors and normal bone marrow using the metabolite choline (Cho) as a marker for malignancy. MATERIALS AND METHODS: Pathologic specimens obtained from 13 patients who had undergone wide resection for skeletal tumors underwent evaluation by MRSI at 1.5 T. Coronal T1-weighted gradient-echo sequence obtained for localization purposes (TR/TE = 250/1.8 msec, field of view [FOV] = 18 x 18), and single-slice MRSI (TR/TE = 2000/272 msec, FOV = 18 x 18, 10-mm slice-thickness) were performed. Water, lipid, and Cho images were reconstructed from MRSI data. Cho signal was measured in each specimen and expressed relative to background noise level (signal-to-noise ratio [SNR]) where noise was measured between 7.0 and 9.0 ppm. Cho SNRs were compared between areas containing malignant tumor and nonmalignant tissue (benign lesion or normal bone marrow) as determined by histopathology. RESULTS: Specimens included 13 skeletal sarcomas (seven osteosarcomas, three chondrosarcomas, one malignant fibrous histiocytoma, one fibrosarcoma, and one leiomyosarcoma). All specimens included a sample of normal bone marrow and two specimens also contained benign lesions. All sarcomas demonstrated a signal at 3.2 ppm assigned to Cho-containing metabolites in areas of malignancy. Peak Cho SNR was significantly different for areas containing histologically-proven malignancy compared to nonmalignant tissue (9.8 +/- 5.1 vs. 2.7 +/- 1.4, respectively, P < 0.002). CONCLUSION: These preliminary results indicate that MRSI at 1.5 T is a promising noninvasive method of differentiating malignant skeletal tumors from nonmalignant tissue. Using MRSI, Cho can be detected in skeletal tumors and may serve as a marker for malignancy.

Bone Neoplasms↗

Proton magnetic resonance spectroscopic imaging to differentiate between nonneoplastic lesions and brain tumors in children.

PURPOSE: To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children. MATERIALS AND METHODS: Thirty-two children (20 males and 12 females, mean age = 10 +/- 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Cho(norm), Cr(norm), and NAA(norm)) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation. RESULTS: Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Cho(norm) (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors. CONCLUSION: Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions.

Adolescent↗

Proton MR spectroscopy in hyperhomocysteinemia with elevated blood methionine levels.

Proton magnetic resonance spectroscopy imaging (MRSI) and serial MRI were performed on a 10-year-old girl with B6 unresponsive cystathionine B-synthase (CBS) deficiency who developed high methionine levels while on betaine therapy. At presentation, T2-weighted sequences showed diffuse white matter (WM) hyperintensity and sulcal effacement, while MRSI metabolite concentrations were normal. Four months later, after the betaine therapy was discontinued and a methionine-restricted diet with vitamin B6, B12, and folate supplementation was initiated, blood methionine levels and MRI findings returned to normal. Normal MRSI at presentation was predictive of a positive outcome despite the markedly abnormal initial MRI results.

Brain↗

Dynamic MR perfusion and proton MR spectroscopic imaging in Sturge-Weber syndrome: correlation with neurological symptoms.

PURPOSE: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status. MATERIALS AND METHODS: Six consecutive patients with a clinically established diagnosis of SWS underwent MRI using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans, dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the neurological scores, and the imaging results were correlated with neurological scores using nonparametric correlation analysis. RESULTS: Two patients had classic neuroimaging findings of unilateral cerebral atrophy with corresponding leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two patients had bilateral disease, and two had normal symmetric perfusion. Among clinical measures, the highest correlation was between hemiparesis index and hypoperfused tissue volume (Spearman's correlation coefficient, rho = 0.943, P < 0.05). There was also a trend of correlation, although not statistically significant (P = 0.06), between the hemiparesis score and the NAA/Cr ratio in the mid to posterior centrum semiovale, lateral gray matter (GM), and splenium. CONCLUSION: In SWS, PWI indicates cerebral hypoperfusion predominantly due to impaired venous drainage, with only the most severely affected regions in some patients also showing arterial perfusion deficiency. The extent and severity of the perfusion abnormality and neuronal loss/dysfunction reflect the severity of neurological symptoms and disability, and the highest correlation is found with the degree of hemiparesis. These parameters may be useful as quantitative measures of disease burden; however, further studies in larger number of patients (and with a more homogeneous age range) are required to confirm the preliminary findings reported here.

Adolescent↗

Optimized detection of lactate at high fields using inner volume saturation.

In localized proton MR spectroscopy ((1)H-MRS) in vivo, the detection of lactate (Lac) is affected by modulation of its resonances due to homonuclear scalar couplings (J). A simple and convenient way to distinguish Lac from lipids is to set the TE to 1/J so that the Lac signal is inverted while other resonances (such as lipid) remain in-phase. However, at high field strengths, such as 3 Tesla or above, the modulation of the Lac signal is complicated by chemical shift effects that cause modulation patterns to vary within different subregions of the localized volume. Under some conditions the Lac signal may even disappear completely. In this note we introduce the concept of inner volume saturation (IVS), which makes use of high bandwidth spatial pulses to remove the signal corresponding to the regions of the localized volume that contribute unwanted modulation patterns. The method is described theoretically and demonstrated experimentally at 3 Tesla in a phantom and a patient with acute stroke. The phantom measurements indicate that virtually 100% of the Lac signal can be recovered using this method. The method should be feasible at magnetic fields above 3 Tesla, and may also be applied to other coupled spin systems in which modulation effects are important.

Aged↗

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.

Animals↗

Correction of symptomatic cerebral malperfusion due to acute type I aortic dissection by transcarotid stenting of the innominate and carotid arteries.

INTRODUCTION: Acute proximal aortic dissection may be complicated by stroke due to malperfusion of the arch vessels. We report a novel case of successful endovascular treatment of acute cerebral malperfusion due to a dissection involving the aortic arch. CASE REPORT: A 66 year old man was transferred from another hospital with an acute type I aortic dissection and underwent emergent repair of the aortic valve and ascending aorta with a composite graft. Left hemiplegia and altered cognitive function were noted on postoperative day 1. A carotid duplex scan showed partial thrombosis of the right carotid artery with very slow flow and reversal of flow in the right vertebral artery. A head CT was normal, while a head MRI and MR angiogram showed intraluminal defects in the inominate and right carotid arteries and perfusion abnormality of the entire right middle cerebral artery territory, but only small infarcts of watershed areas. The patient underwent stenting of the right carotid and inominate arteries through the right carotid artery with complete resolution of a large pressure gradient that was noted prior to stenting. The patient's left hemiplegia and cognitive impairment subsequently resolved during his inpatient hospitalization. On follow up five months later, he had a normal neurologic exam and MRI showed old watershed infarcts but no perfusion abnormality. On most recent follow-up 2.5 years after treatment, he remains well and a CT angiogram shows that his stented vessels remain patent. CONCLUSION: Endovascular techniques may be safely applied to correct cerebral malperfusion that results from type I aortic dissection.

Acute Disease↗

Neuroimaging of phakomatoses.

The phakomatoses are congenital disorders manifesting with central nervous system and cutaneous abnormalities. The structures predominantly affected are those of ectodermal origin, including the skin, nervous system, and eyes. The 4 most common phakomatoses are neurofibromatosis (types 1 and 2), tuberous sclerosis, Sturge-Weber disease, and von Hippel-Lindau disease. Imaging of the brain and spine in these disorders plays an important role in diagnosis, as well as determining the extent of involvement and guiding surgical interventions. This article reviews the application of x-ray computed tomography and magnetic resonance imaging to these disorders, as well as that of newer, "functional" imaging techniques such as positron emission tomography, magnetic resonance perfusion imaging, and spectroscopy.

Central Nervous System↗

Neural correlates of modality-specific spatial extinction.

Sites of lesions responsible for visual, tactile, and/or motor extinction have not been clearly identified. We sought to determine the frequency of extinction in various modalities immediately after acute ischemic stroke, the rate of co-occurrence of extinction across modalities, and areas of infarct and/or hypoperfusion associated with each modality of extinction. A total of 148 patients with right supratentorial stroke were studied. In Study 1, 88 patients without hemiplegia, hemianesthesia, or visual field cuts were tested within 24 hours of onset for visual, tactile, and motor extinction, and underwent magnetic resonance diffusion and perfusion imaging. Associations between modality of extinction and areas of neural dysfunction (hypoperfusion/infarct) were identified. Of the 88 patients, 19 had only tactile extinction, 8 had only visual extinction, 12 had only motor extinction, 14 had extinction in two or more modalities, and 35 had no extinction. Tactile extinction was associated with neural dysfunction in the inferior parietal lobule; visual extinction was associated with dysfunction in the visual association cortex; and motor extinction was associated with neural dysfunction in the superior temporal gyrus. In Study 2, data from 60 patients who were excluded from Study 1 because of motor deficits were analyzed in the same way to determine whether frontal lesions contributed to visual or tactile extinction. Results again demonstrated that tactile extinction is associated with inferior parietal dysfunction, and visual extinction is associated with dysfunction of the visual association cortex. Potential accounts of the results, based on the "hemisphere rivalry" model of extinction and the limited attentional capacity model, are considered.

Aged↗

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.

Adolescent↗

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.

Adult↗

Diffusion tensor-based imaging reveals occult abnormalities in adrenomyeloneuropathy.

"Pure" adrenomyeloneuropathy (AMN) is the noninflammatory myeloneuropathic variant of X-linked adrenoleukodystrophy, where the disease process appears to be restricted to spinal cord tracts and peripheral nerves. The absence of obvious brain involvement makes it distinct from the inflammatory cerebral phenotypes of X-linked adrenoleukodystrophy. However, some pure AMN patients later experience development of cerebral demyelination, but little is known about the extent of brain involvement in pure AMN patients who have normal brain magnetic resonance imaging. We used diffusion tensor imaging to investigate possible occult cerebral abnormalities in such pure AMN patients. Fractional anisotropy and trace were studied in three-dimensional reconstructions of white matter tracts commonly involved in cerebral phenotypes of X-linked adrenoleukodystrophy. Results demonstrated reduced fractional anisotropy and increased trace in bilateral corticospinal tracts and genu of corpus callosum (p < 0.05). Diffusion tensor imaging-based three-dimensional fiber tracking showed occult tract-specific cerebral microstructural abnormalities in pure AMN patients who had a normal conventional brain magnetic resonance image. Corticospinal tract abnormalities could reflect a centripetal extension of spinal cord long-tract distal axonopathy. Accompanying abnormalities in genu of corpus callosum indicate that the disease pathology in pure AMN may not be limited to spinal cord long tracts alone, although the involvement of the latter is most prominent and severe.

Adrenoleukodystrophy↗