Barbara A. Holshouser

Diffuse axonal injury in children: Clinical correlation with hemorrhagic lesions

An inception cohort of 40 children and adolescents with traumatic brain injury and suspected diffuse axonal injury were studied using a new high‐resolution magnetic resonance imaging susceptibility‐weighted technique that is very sensitive for hemorrhage. A blinded comparison was performed between the extent of parenchymal hemorrhage and initial clinical variables as well as outcomes measured at 6 to 12 months after injury. Children with lower Glasgow Coma Scale scores (≤8, n = 30) or prolonged coma (>4 days, n = 20) had a greater average number (p = 0.007) and volume (p = 0.008) of hemorrhagic lesions. Children with normal outcomes or mild disability (n = 30) at 6 to 12 months had, on average, fewer hemorrhagic lesions (p = 0.003) and lower volume (p = 0.003) of lesions than those who were moderately or severely disabled or in a vegetative state. Significant differences also were observed when comparing regional injury to clinical variables. Because susceptibility‐weighted imaging is much more sensitive than conventional T2*‐weighted gradient‐echo sequences in detecting hemorrhagic diffuse axonal injury, more accurate and objective assessment of injury can be obtained early after insult, and may provide better prognostic information regarding duration of coma as well as long‐term outcome. Ann Neurol 2004;56:36–50

Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study

Neuroimaging with iron-sensitive MR sequences [gradient echo T2* and susceptibility-weighted imaging (SWI)] identifies small signal voids that are suspected brain microbleeds. Though the clinical significance of these lesions remains uncertain, their distribution and prevalence correlates with cerebral amyloid angiopathy (CAA), hypertension, smoking, and cognitive deficits. Investigation of the pathologies that produce signal voids is necessary to properly interpret these imaging findings. We conducted a systematic correlation of SWI-identified hypointensities to tissue pathology in postmortem brains with Alzheimer’s disease (AD) and varying degrees of CAA. Autopsied brains from eight AD patients, six of which showed advanced CAA, were imaged at 3T; foci corresponding to hypointensities were identified and studied histologically. A variety of lesions was detected; the most common lesions were acute microhemorrhage, hemosiderin residua of old hemorrhages, and small lacunes ringed by hemosiderin. In lesions where the bleeding vessel could be identified, β-amyloid immunohistochemistry confirmed the presence of β-amyloid in the vessel wall. Significant cellular apoptosis was noted in the perifocal region of recent bleeds along with heme oxygenase 1 activity and late complement activation. Acutely extravasated blood and hemosiderin were noted to migrate through enlarged Virchow–Robin spaces propagating an inflammatory reaction along the local microvasculature; a mechanism that may contribute to the formation of lacunar infarcts. Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease.

Reliability in detection of hemorrhage in acute stroke by a new three-dimensional gradient recalled echo susceptibility-weighted imaging technique compared to computed tomography: A retrospective study

To compare the sensitivity of magnetic resonance (MR) susceptibility‐weighted imaging (SWI) with conventional MR sequences and computed tomography (CT) in the detection of hemorrhage in an acute infarct.

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.

Serial susceptibility weighted MRI measures brain iron and microbleeds in dementia.

A new iron sensitive MR sequence (susceptibility weighted imaging - SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n = 73) and cognitively normal participants (n = 33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of BMB were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p = 0.035) and stable MCI (p = 0.01). BMB were detected in 9 out of 26 (38%) MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants [risk ratio = 2.06 (95% confidence interval 1.37-3.12)]. SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR-based biomarkers for neurodegenerative diseases.

Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury

We studied 26 infants (1-18 months old) and 27 children (18 months or older) with acute nonaccidental (n = 21) or other forms (n = 32) of traumatic brain injury using clinical rating scales, a 15-point MRI scoring system, and occipital gray matter short-echo proton MRS. We compared the differences between the acutely determined variables (metabolite ratios and the presence of lactate) and 6- to 12-month outcomes. The metabolite ratios were abnormal (lower NAA/Cre or NAA/Cho; higher Cho/Cre) in patients with a poor outcome. Lactate was evident in 91% of infants and 80% of children with poor outcomes; none of the patients with a good outcome had lactate. At best, the clinical variables alone predicted the outcome in 77% of infants and 86% of children, and lactate alone predicted the outcome in 96% of infants and 96% of children. No further improvement in outcome prediction was observed when the lactate variable was combined with MRI ratios or clinical variables. The findings of spectral sampling in areas of brain not directly injured reflected the effects of global metabolic changes. Proton MRS provides objective data early after traumatic brain injury that can improve the ability to predict long-term neurologic outcome.

The role of advanced MR imaging findings as biomarkers of traumatic brain injury.

Treatment of traumatic brain injury (TBI) requires proper classification of the pathophysiology. Clinical classifiers and conventional neuroimaging are limited in TBI detection, outcome prediction, and treatment guidance. Advanced magnetic resonance imaging (MRI) techniques such as susceptibility weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopic imaging are sensitive to microhemorrhages, white matter injury, and abnormal metabolic activities, respectively, in brain injury. In this article, we reviewed these 3 advanced MRI methods and their applications in TBI and report some new findings from our research. These MRI techniques have already demonstrated their potential to improve TBI detection and outcome prediction. As such, they have demonstrated the capacity of serving as a set of biomarkers to reveal the heterogeneous and complex nature of brain injury in a regional and temporal manner. Further longitudinal studies using advanced MRI in a synergistic approach are expected to provide insight in understanding TBI and imaging implications for treatment.

MR spectroscopy: Predicting long-term neuropsychological outcome following pediatric TBI

To identify useful acute indicators of long‐term neurocognitive outcome beyond clinical variables for children and adolescents treated for a traumatic brain injury (TBI).

Prospective Longitudinal Proton Magnetic Resonance Spectroscopic Imaging in Adult Traumatic Brain Injury

To investigate whether longitudinal magnetic resonance proton spectroscopic imaging (MRSI) demonstrates regional metabolite abnormalities after traumatic brain injury (TBI) that predict long‐term neurologic outcome.

Prognostic value of 1H-MRS in perinatal CNS insults

The authors studied 37 term neonates (38-42 gestational weeks) at 1-11 days after central nervous system insult to determine whether proton magnetic resonance spectroscopy (1H-MRS) of the occipital gray/parietal white matter was useful in predicting outcomes. Etiologies included asphyxia, 18; sepsis/meningitis, 8; metabolic disorders, 5; stroke, 4; and trauma, 2. 1H-MRS data (1.5T; 8 cm3 vol, stimulated echo acquisition mode sequence, TE = 20 ms, TR = 3000 ms) were expressed as metabolite peak area ratios (NAA/Cr, NAA/Cho, Cho/Cr) and the presence or absence of lactate. Outcomes were assessed at 6 to 12 months post-insult using the Pediatric Cerebral Performance Scale and were dichotomized as follows: good/moderate outcome (good, mild or moderate disability) or poor outcome (severe disability, persistent vegetative state, death). Neonates with poor outcomes had significantly lower NAA/Cho and significantly higher Cho/Cr ratios in the occipital region, as compared with patients with good/moderate outcomes. No neonates with good/moderate outcomes had metabolite ratios that exceeded 2 standard deviations from the mean. In addition, the absence of lactate on 1H-MRS correlated with a good/moderate outcome. The study also showed that 1H-MRS metabolite ratio data, added to either the Sarnat or EEG scores, enhanced the correlation between these prognostic factors and outcomes. 1H-MRS provides additional objective data early after a wide variety of perinatal neurologic insults to enhance outcome prediction.