Quantitative susceptibility mapping as a measure of cerebral oxygenation in neonatal piglets.

Prominence of cerebral veins using susceptibility weighted magnetic resonance imaging (SWI) has been used as a qualitative indicator of cerebral venous oxygenation (CvO2). Quantitative susceptibility mapping (QSM) adds more precision to the assessment of CvO2, but has not been applied to neonatal hypoxic ischemic injury (HII). We proposed to study QSM measures of venous susceptibility and their correlation with direct measures of brain oxygenation and cerebral blood flow (CBF) in the neonatal piglet. The association of QSM intravascular cerebral venous susceptibility, with brain tissue O2 tension, CBF, cortical tissue oxyhemoglobin saturation, and the partial pressure of oxygen in arterial blood measurement during various oxygenation states was determined by linear regression. Compared to normoxia, venous susceptibility in the straight sinus increased 56.8 ± 25.4% during hypoxia, while decreasing during hyperoxia (23.5 ± 32.9%) and hypercapnia (23.3 ± 73.1%), which was highly correlated to all other measures of oxygenation (p < 0.0001) but did not correlate to CBF (p = 0.82). These findings demonstrate a strong relationship between venous susceptibility and brain tissue O2 tension. Our results suggest that QSM-derived venous susceptibility is sensitive to cerebral oxygenation status across various oxygenation states.

Cerebral Microhemorrhage: A Frequent Magnetic Resonance Imaging Finding in Pediatric Patients after Cardiopulmonary Bypass.

OBJECTIVES: This study was undertaken to estimate the incidence and burden of cerebral microhemorrhage (CM) in patients with heart disease who underwent cardiopulmonary bypass (CPB), as detected on susceptibility-weighted imaging (SWI), a magnetic resonance (MR) sequence that is highly sensitive to hemorrhagic products. MATERIALS AND METHODS: With Institutional Review Board waiver of consent, MR imaging (MRI) of a cohort of 86 consecutive pediatric patients with heart failure who underwent heart transplantation evaluation were retrospectively reviewed for CM. A nested case-control study was performed. The CPB group consisted of 23 pediatric patients with heart failure from various cardiac conditions who underwent CPB. The control group was comprised of 13 pediatric patients with similar cardiac conditions, but without CPB history. Ten patients in the CPB group were female (age: 5 days to 16 years at the time of the CPB and 6 days to 17 years at the time of the MRI). The time interval between the CPB and MRI ranged from 11 days to 4 years and 5 months. Six patients in the control group were female, age range of 2 days to 6 years old. The number of CM on SWI was counted by three radiologists (PK, EK and DK). The differences in number of CM between groups were tested for significance using Mann-Whitney U-test, α = 0.05. Using the univariate analysis of variance model, the differences in number of CM between groups were also tested with adjustment for age at MRI. RESULTS: There are statistically significant differences in CM on SWI between the CPB group and control group with more CM were observed in the CPB group without and with adjustment for age at MRI (P < 0.001). CONCLUSIONS: Exposure of CPB is associated with increased prevalence and burden of CM among pediatric patients with heart failure.

Hypoxic-ischemic injury: utility of susceptibility-weighted imaging.

Magnetic resonance imaging is increasingly used to assess neonatal hypoxic-ischemic injury, and several scoring systems were developed to predict neurologic outcomes in these patients. We examined the magnetic resonance imaging studies of 33 neonates/infants who manifested acute perinatal hypoxic-ischemic injuries. Using a seven-point susceptibility-weighted imaging categorical grading scale, each patient received a "prominence of vein" score, which was dichotomized into a "normal" or "abnormal" group. Six-month outcomes were assessed using the Pediatric Cerebral Performance Category Scale. We then determined whether "prominence of vein" scores correlated with neurologic outcomes in patients with hypoxic-ischemic injuries, and compared these results with the Barkovich magnetic resonance imaging scoring system. Patients with "normal" "prominence of vein" scores demonstrated better outcomes (mean Pediatric Cerebral Performance Category Scale value = 2) than patients with "abnormal" "prominence of vein" scores (mean Pediatric Cerebral Performance Category Scale value = 4). The dichotomized "prominence of vein" groups demonstrated correlations with the Barkovich magnetic resonance imaging scores of the proton density-weighted basal ganglia, watershed, and combined basal ganglia/watershed regions. The susceptibility-weighted imaging categorical grading scale may aid in predicting neurologic outcomes after hypoxic-ischemic injuries.

White matter microsusceptibility changes in patients with hepatic encephalopathy.

We report a new radiological finding in two patients with hepatic encephalopathy. A new susceptibility-weighted (SWI) magnetic resonance imaging sequence revealed multiple bilateral microsusceptibility changes in the corpus callosum and white matter, while the conventional T1 and T2 weighted images were unremarkable. We postulate that the etiology of the microsusceptibility changes may be related to hepatic coagulopathy and other factors, such as impaired cerebral blood flow and brain edema.

Value of cerebral microhemorrhages detected with susceptibility-weighted MR Imaging for prediction of long-term outcome in children with nonaccidental trauma.

PURPOSE: To determine the prevalence of parenchymal brain microhemorrhages (MHs) in infants with nonaccidental trauma (NAT) by using susceptibility-weighted (SW) magnetic resonance (MR) imaging and to assess whether the presence of MH results in improved prediction of the long-term neurologic outcome. MATERIALS AND METHODS: A retrospective case-control analysis of the data for 101 children aged 1-32 months with forensic pediatric specialist-confirmed NAT was performed with institutional review board approval. Sixty-two patients were boys (mean age, 8.4 months +/- 7.4 [standard deviation]), and 39 were girls (mean age, 7.4 months +/- 7.8). The imaging findings and clinical data of the children who were examined with SW imaging were collected. Exclusion criteria included pre-existing cognitive delays, central nervous system malformations, previous brain injuries, and/or birth before 30 weeks gestation. Dichotomized long-term neurologic outcomes (good [normal, mild disability, or moderate disability] versus poor [severe disability, vegetative state, or death]) at greater than or equal to 6 months (mean, 33 months; range 6-95 months) were available for 53 patients (36 boys [mean age, 7.3 months +/- 5.9]; 17 girls [mean age, 7.4 months +/- 7.9]; overall range, 2-32 months). Logistic regression was used to determine whether the presence of SW imaging-depicted MH, as compared with other radiologic findings, resulted in improved prediction of long-term neurologic outcome. RESULTS: Imaging findings showed that of the 101 patients, 29 (29%) had MH at SW imaging, 66 (65%) had extraaxial hemorrhages, 52 (51%) had retinal hemorrhages, and 35 (35%) had evidence of acute ischemic injury. A significantly larger number of children with poor outcomes than children with good outcomes had brain MH (nine of 14 vs seven of 39; P = .001) and ischemic injury (13 of 14 vs 17 of 39; P = .006). Logistic regression analysis revealed presence of MH at SW imaging-followed by acute ischemic injury, initial Glasgow Coma Scale score, and age-to be the most significant single variable in the final model, with an overall predictive accuracy of 92.5%. CONCLUSION: Presence of intraparenchymal brain MH in children with NAT, as detected on SW images, correlates with significantly poor long-term neurologic outcome, improves outcome prediction compared with the predictions made by using other tested clinical and imaging findings, and is most predictive when combined with presence of ischemic injury.

Magnetic resonance spectroscopy predicts outcomes for children with nonaccidental trauma.

OBJECTIVE: We evaluated proton magnetic resonance spectroscopic imaging (MRSI) findings for children with traumatic brain injury attributable to nonaccidental trauma (NAT) early after injury, to determine whether brain metabolite changes predicted outcomes. METHODS: Proton MRSI (1.5 T) was performed (mean: 5 days after injury [range: 1-30 days]) through the level of the corpus callosum for 90 children with confirmed NAT. Regional N-acetylaspartate/total creatine, N-acetylaspartate/total choline, and choline/creatine ratios and the presence of lactate were measured. Data on long-term outcomes defined at > or =6 months were collected for 44 of 90 infants. We grouped patients into good (normal, mild disability, or moderate disability; n = 32) and poor (severe disability, vegetative state, or dead; n = 12) outcome groups. RESULTS: We found that N-acetylaspartate/creatine and N-acetylaspartate/choline ratios (mean total, corpus callosum, and frontal white matter) were significantly decreased in patients with poor outcomes (P < .001). A logistic regression model using age, initial Glasgow Coma Scale score, presence of retinal hemorrhage, lactate on MRSI scans, and mean total N-acetylaspartate/creatine ratio predicted outcomes accurately in 100% of cases. CONCLUSIONS: Reduced N-acetylaspartate levels (ie, neuronal loss/dysfunction) and elevated lactate levels (altered energy metabolism) correlated with poor neurologic outcomes for infants with NAT. Elevated lactate levels may reflect primary or secondary hypoxic-ischemic injury, which may occur with NAT. Our data suggest that MRSI performed early after injury can be used for long-term prognosis.

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, ß-amyloid immunohistochemistry confirmed the presence of ß-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 Virchow­Robin 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.

Imaging cerebral microbleeds using susceptibility weighted imaging: one step toward detecting vascular dementia.

PURPOSE: To monitor changes in the number of cerebral microbleeds (CMBs) in a longitudinal study of healthy controls (HC) and mild-cognitively impaired (MCI) patients using susceptibility weighted imaging (SWI). MATERIALS AND METHODS: SWI was used to image 28 HC and 75 MCI patients annually at 1.5 Tesla over a 4-year period. Magnitude and phase data were used to visualize CMBs for the first and last scans of 103 subjects. RESULTS: Preliminary analysis revealed that none of the 28 HC had more than three CMBs. In the 75 MCI patients, five subjects had more than three CMBs in both first and last scans, while one subject had more than three bleeds only in the last scan. In five of these six MCI patients, the number of CMBs increased over time and all six went on to develop progressive cognitive impairment (PCI). Of the 130 total CMBs seen in the last scans of the six MCI cases, most were less than 4 mm in diameter. CONCLUSION: SWI can reveal small CMBs on the order of 1 mm in diameter and this technique can be used to follow their development longitudinally. Monitoring CMBs may be a means by which to evaluate patients for the presence of microvascular disease that leads to PCI.

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.

Susceptibility-Weighted Magnetic Resonance Imaging in the Evaluation of Dementia.

An 88-year-old woman with a clinical diagnosis of Alzheimer's disease and advanced dementia, was evaluated with standard MRI of the brain as well as Susceptibility Weighted Imaging (SWI) with the MRI. SWI revealed more extensive brain microhemorrhages than standard MRI techniques, allowing the radiologic diagnosis of cerebral amyloid angiopathy. SWI shows promise as a more sensitive diagnostic tool than standard brain MRI for the evaluation of patients with dementia.

Clinical applications of neuroimaging with susceptibility-weighted imaging.

Susceptibility-weighted imaging (SWI) consists of using both magnitude and phase images from a high-resolution, three-dimensional, fully velocity compensated gradient-echo sequence. Postprocessing is applied to the magnitude image by means of a phase mask to increase the conspicuity of the veins and other sources of susceptibility effects. This article gives a background of the SWI technique and describes its role in clinical neuroimaging. SWI is currently being tested in a number of centers worldwide as an emerging technique to improve the diagnosis of neurological trauma, brain neoplasms, and neurovascular diseases because of its ability to reveal vascular abnormalities and microbleeds.

Symptomatic protocols for adult tethered cord syndrome.

Diagnosis of tethered cord syndrome (TCS) is complicated because anatomical information is not adequate for this task. For example, recent studies have shown that the combination of an elongated cord and a thick filum terminale, demonstrated by MRI or at operation, is no longer an essential feature for the diagnosis of TCS. For TCS diagnosis, emphasis should rather be on its characteristic symptomatology and accentuated by postural changes, since TCS is a functional disorder of the lumbosacral spinal cord. In this report, the authors present the list of signs and symptoms pertinent to TCS in adult and late teenage patients to serve as a diagnostic means.

Proton spectroscopy detected myoinositol in children with traumatic brain injury.

Previous studies have shown that proton magnetic resonance spectroscopy (MRS) is useful in predicting neurologic prognosis in children with traumatic brain injury (TBI). Reductions in N-acetyl derived metabolites and presence of lactate have been predictive of poor outcomes. We examined another spectroscopy metabolite, myoinositol (mI), to determine whether it is altered after TBI. Found primarily in astrocytes, mI functions as an osmolyte and is involved in hormone response pathways and protein-kinase C activation. Myoinositol is elevated in the newborn brain and is increased in a variety of diseases. We studied 38 children (mean age 11 y; range 1.6-17 y) with TBI using quantitative short echo time occipital gray and parietal white matter proton MRS at a mean of 7 d (range 1-17 d) after injury. We found that occipital gray matter mI levels were increased in children with TBI (4.30 +/- 0.73) compared with controls (3.53 +/- 0.48; p = 0.003). We also found that patients with poor outcomes 6-12 mo after injury had higher mI levels (4.78 +/- 0.68) than patients with good outcomes (4.15 +/- 0.69; p < 0.05). Myoinositol is elevated after pediatric TBI and is associated with a poor neurologic outcome. The reasons for its elevation remain unclear but may be due to astrogliosis or to a disturbance in osmotic function.

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.

PURPOSE: 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. MATERIALS AND METHODS: A series of 84 patients suspected of having acute strokes had both CT and MR imaging (MRI) scans with diffusion-weighted imaging (DWI) and SWI. The SWI sequence is a new high-resolution three-dimensional (3D) imaging technique that amplifies phase to enhance the magnitude contrast. RESULTS: Thirty-eight of 84 cases showed abnormal DWI consistent with acute infarct. Of the 38, SWI showed evidence of hemorrhage in 16 cases, compared to eight cases with spin echo (SE) T2, seven cases with fluid attentuated inversion recovery (FLAIR), and only five cases with CT. In a subset of 17 cases of acute infarct who had both two-dimensional gradient recalled echo (2D-GRE) T2*-weighted imaging and SWI, in addition to conventional MRI, evidence of hemorrhage was seen in 10 cases using SWI, compared to seven cases with 2D-GRE T2*. CONCLUSION: SWI proved to be a powerful new approach for visualizing hemorrhage in acute stroke compared to CT and conventional MRI methods.

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 (< or =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.

How different MR imaging criteria relate to the diagnosis of multiple sclerosis and its outcome.

This article reviews the evolution of MR imaging criteria used to diagnose multiple sclerosis (MS) over the past decade and a half to help demonstrate how these changes have influenced the sensitivity and specificity of diagnosing and treating patients with MS. The article discusses the benefits and drawbacks of making very specific diagnoses versus sensitive but less specific diagnoses. In addition, the application of these various diagnostic criteria to patient outcomes and clinical trials is reviewed.

Hemorrhagic shearing lesions in children and adolescents with posttraumatic diffuse axonal injury: improved detection and initial results.

PURPOSE: To compare the effectiveness of a high-spatial-resolution susceptibility-weighted (SW) magnetic resonance (MR) imaging technique with that of a conventional gradient-recalled-echo (GRE) MR imaging technique for detection of hemorrhage in children and adolescents with diffuse axonal injury (DAI). MATERIALS AND METHODS: Seven young patients with a mean Glasgow Coma Scale score of 7 +/- 4 (SD) at admission were imaged a mean of 5 days +/- 3 after injury. High-spatial-resolution three-dimensional GRE imaging performed with postprocessing by using a normalized phase mask was compared with conventional GRE MR imaging. The total and mean values of lesion number and apparent hemorrhage volume load determined with both examinations were compared. Mean values were compared by using paired t test analysis. Differences were considered to be significant at P < or =.05. RESULTS: Hemorrhagic lesions were much more visible on SW MR images than on conventional GRE MR images. SW MR imaging depicted 1,038 hemorrhagic DAI lesions with an apparent total hemorrhage volume of 57,946 mm3. GRE MR imaging depicted 162 lesions with an apparent total hemorrhage volume of 28,893 mm3. SW MR imaging depicted a significantly higher mean number of lesions in all patients than did GRE MR imaging, according to results of visual (P =.004) and computer (P =.004) counting analyses. The mean hemorrhage volume load for all patients also was significantly greater (P =.014) by using SW MR imaging according to computer analysis. SW MR imaging appeared to depict much smaller hemorrhagic lesions than GRE MR imaging. The majority (59%) of individual hemorrhagic DAI lesions seen on SW MR images were small in area (<10 mm(2)), whereas the majority (43%) of lesions seen on GRE images were larger in area (10-20 mm(2)). CONCLUSION: SW MR imaging depicts significantly more small hemorrhagic lesions than does conventional GRE MR imaging and therefore has the potential to improve diagnosis of DAI.