Manohar Shroff

Principles, techniques, and applications of T2*-based MR imaging and its special applications.

T2* relaxation refers to decay of transverse magnetization caused by a combination of spin-spin relaxation and magnetic field inhomogeneity. T2* relaxation is seen only with gradient-echo (GRE) imaging because transverse relaxation caused by magnetic field inhomogeneities is eliminated by the 180 degrees pulse at spin-echo imaging. T2* relaxation is one of the main determinants of image contrast with GRE sequences and forms the basis for many magnetic resonance (MR) applications, such as susceptibility-weighted (SW) imaging, perfusion MR imaging, and functional MR imaging. GRE sequences can be made predominantly T2* weighted by using a low flip angle, long echo time, and long repetition time. GRE sequences with T2*-based contrast are used to depict hemorrhage, calcification, and iron deposition in various tissues and lesions. SW imaging uses phase information in addition to T2*-based contrast to exploit the magnetic susceptibility differences of the blood and of iron and calcification in various tissues. Perfusion MR imaging exploits the signal intensity decrease that occurs with the passage of a high concentration of gadopentetate dimeglumine through the microvasculature. Change in oxygen saturation during specific tasks changes the local T2*, which leads to the blood oxygen level-dependent effect seen at functional MR imaging. The basics of T2* relaxation, T2*-weighted sequences, and their clinical applications are presented, followed by the principles, techniques, and clinical uses of four T2*-based applications, including SW imaging, perfusion MR imaging, functional MR imaging, and iron overload imaging.

Role of MRI in the differentiation of ADEM from MS in children

Background: Acute disseminated encephalomyelitis (ADEM) is typically a monophasic demyelinating disorder. However, a clinical presentation consistent with ADEM can also be the first manifestation of multiple sclerosis (MS), particularly in children. Quantitative analyses of MRI images from children with monophasic ADEM have yet to be compared with those from children with MS, and MRI criteria capable of distinguishing ADEM from MS at onset have yet to be derived. Methods: A retrospective analysis of MRI scans obtained at first attack from 28 children subsequently diagnosed with MS and 20 children with ADEM was performed. T2/fluid-attenuated inversion recovery hyperintense lesions were quantified and categorized according to location, description, and size. T1-weighted images before and after administration of gadolinium were evaluated for the presence of black holes and for gadolinium enhancement. Mean lesion counts and qualitative features were compared between groups and analyzed to create a proposed diagnostic model. Results: Total lesion number did not differentiate ADEM from MS, but periventricular lesions were more frequent in children with MS. Combined quantitative and qualitative analyses led to the following criteria to distinguish MS from ADEM: any two of 1) absence of a diffuse bilateral lesion pattern, 2) presence of black holes, and 3) presence of two or more periventricular lesions. Using these criteria, MS patients at first attack could be distinguished from monophasic ADEM patients with an 81% sensitivity and a 95% specificity. Conclusions: MRI diagnostic criteria are proposed that may be useful in differentiating children experiencing the first attack of multiple sclerosis from those with monophasic acute disseminated encephalomyelitis.

MEG Predicts Outcome Following Surgery for Intractable Epilepsy in Children with Normal or Nonfocal MRI Findings

Summary:  Purpose: To identify the predictors of postsurgical seizure freedom in children with refractory epilepsy and normal or nonfocal MRI findings.

Steady-State MR Imaging Sequences: Physics, Classification, and Clinical Applications

Steady-state sequences are a class of rapid magnetic resonance (MR) imaging techniques based on fast gradient-echo acquisitions in which both longitudinal magnetization (LM) and transverse magnetization (TM) are kept constant. Both LM and TM reach a nonzero steady state through the use of a repetition time that is shorter than the T2 relaxation time of tissue. When TM is maintained as multiple radiofrequency excitation pulses are applied, two types of signal are formed once steady state is reached: preexcitation signal (S-) from echo reformation; and postexcitation signal (S+), which consists of free induction decay. Depending on the signal sampled and used to form an image, steady-state sequences can be classified as (a) postexcitation refocused (only S+ is sampled), (b) preexcitation refocused (only S- is sampled), and (c) fully refocused (both S+ and S- are sampled) sequences. All tissues with a reasonably long T2 relaxation time will show additional signals due to various refocused echo paths. Steady-state sequences have revolutionized cardiac imaging and have become the standard for anatomic functional cardiac imaging and for the assessment of myocardial viability because of their good signal-to-noise ratio and contrast-to-noise ratio and increased speed of acquisition. They are also useful in abdominal and fetal imaging and hold promise for interventional MR imaging. Because steady-state sequences are now commonly used in MR imaging, radiologists will benefit from understanding the underlying physics, classification, and clinical applications of these sequences.

Presumed perinatal ischemic stroke: Vascular classification predicts outcomes

Perinatal stroke commonly causes childhood neurological morbidity. Presumed perinatal ischemic stroke (PPIS) defines children presenting outside a normal perinatal period with chronic, focal infarction on neuroimaging. Infarcts are assumed to represent arterial strokes, but recent evidence suggests the periventricular venous infarction (PVI) of infants born preterm may also occur in utero and present as PPIS. Using the largest published cohort, we aimed to define arterial and PVI PPIS syndromes and their outcomes.

The clinical features, MRI findings, and outcome of optic neuritis in children

Background: Optic neuritis (ON) in childhood is thought to be more likely bilateral and less likely to lead to multiple sclerosis (MS) vs ON in adults. Methods: The authors evaluated clinical features, maximal visual deficit and recovery, visual evoked potentials (VEPs), neuroimaging, and outcome in a cohort of children with ON. Results: Records of 36 children (female/male ratio 1.6), ages 2.2 to 17.8 (mean 12.2) years, were reviewed. ON was unilateral in 58% and bilateral in 42%. Maximal visual deficit was severe in 69%, but full recovery occurred in 39 of 47 affected eyes (83%). VEPs were abnormal in 88%. Neurologic abnormalities in addition to those associated with ON were documented in 13 children. Neuroimaging studies of the optic nerve were abnormal in 55%. Brain MRI in 35 children demonstrated white matter lesions separate from the optic nerves in 54%. Follow-up is 2.4 years (0.3 to 8.3 years). To date, 13 children (36%) have been diagnosed with MS and 1 has Devic disease. Bilateral ON was more likely to be associated with MS outcome (p = 0.03). All 13 children with MS had white matter lesions on brain MRI. None of the children with a normal brain MRI have developed MS to date. Conclusions: Contrary to expectations, optic neuritis (ON) in childhood was more likely to be unilateral, multiple sclerosis (MS) risk was high (36% at 2 years), and bilateral rather than unilateral ON was associated with a greater likelihood of MS. Clinical findings extrinsic to the visual system on baseline examination (p < 0.0001) and MRI evidence of white matter lesions outside the optic nerves (p < 0.0001) were strongly correlated with MS outcome.

Quantified Corticospinal Tract Diffusion Restriction Predicts Neonatal Stroke Outcome

Background and Purpose— Neonatal arterial ischemic stroke occurs in ≥1:4000 births. Many children experience motor deficits but acute predictors of outcome are lacking. Diffusion-weighted MRI changes in descending corticospinal tracts remote from arterial ischemic stroke may represent pre-Wallerian degeneration. We verify and quantify this signal and correlate it with motor outcome. Methods— Fourteen neonates with acute arterial ischemic stroke and ≥12 months follow-up with the Pediatric Stroke Outcome Measure were included. Quantitative measurements of descending corticospinal tracts diffusion-weighted MRI signal were developed using Image J software. Results— Ipsilesional descending corticospinal tract diffusion-weighted MRI signal was abnormal in 10 neonates with decreased apparent diffusion coefficients (P<0.001). Poor outcome correlated with: (1) percentage of peduncle (P=0.002); (2) length of descending corticospinal tracts P<0.001); and (3) volume of descending corticospinal tracts (P=0.002). None of: (1) any peduncle; (2) any posterior limb of the internal capsule; or (3) infarct volume correlated with outcome. All children without descending corticospinal tracts signal had normal outcome. Chronic Wallerian degeneration was seen in all children with hemiparesis. Software-assisted analysis was superior to visual inspection with excellent reliability (intra-class correlation coefficient ≥0.9). Conclusion— Descending corticospinal tracts diffusion-weighted MRI signal is predictive of motor outcome from neonatal arterial ischemic stroke. This accurate, reliable, and simple tool will impact decision making in acute neonatal stroke.

Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study.

Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonates and children increasingly receive anticoagulant therapy (ACT) based on adult studies. Safety data for ACT in pediatric CSVT are scant and urgently needed. The objective was to assess the safety and outcome of ACT in pediatric CSVT.

MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study

BACKGROUND Multiple sclerosis (MS) diagnostic criteria incorporate MRI features that can be used to predict later diagnosis of MS in adults with acute CNS demyelination. To identify MRI predictors of a subsequent MS diagnosis in a paediatric population, we created a standardised scoring method and applied it to MRI scans from a national prospective incidence cohort of children with CNS demyelination. METHODS Clinical and MRI examinations were done at the onset of acute CNS demyelination and every 3 months in the first year after that, and at the time of a second demyelinating attack. MS was diagnosed on the basis of clinical or MRI evidence of relapsing disease. Baseline MRI scans were assessed for the presence of 14 binary response parameters. Parameters were assessed with a multiple tetrachoric correlation matrix. Univariate analyses and multivariable Cox proportional hazards models were used to identify predictors of MS. FINDINGS Between Sept 1, 2004, and June 30, 2010, 332 children and adolescents were assessed for eligibility. 1139 scans were available from 284 eligible participants who had been followed up for 3·9 (SD 1·7) years. 57 (20%) were diagnosed with MS after a median of 188 (IQR 144-337) days. Seven of 14 binary response parameters were retained. The presence of either one or more T1-weighted hypointense lesions (hazard ratio 20·6, 95% CI 5·46-78·0) or one or more periventricular lesions (3·34, 1·27-8·83) was associated with an increased likelihood of MS diagnosis (sensitivity 84%, specificity 93%, positive predictive value 76%, negative predictive value 96%). Risk for MS diagnosis was highest when both parameters were present (34·27, 16·69-70·38). Although the presence of contrast enhancement, cerebral white matter, intracallosal, and brainstem lesions was associated with MS in the univariate analyses, these parameters were not retained in the multivariable models. INTERPRETATION Specific MRI parameters can be used to predict diagnosis of MS in children with incident demyelination of the CNS. The ability to promptly identify children with MS will enhance timely access to care and will be important for future clinical trials in paediatric MS. FUNDING Canadian Multiple Sclerosis Scientific Research Foundation.

Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma

PURPOSE To evaluate the efficacy of single-agent vinblastine in pediatric patients with recurrent or refractory low-grade glioma. PATIENTS AND METHODS Patients were eligible if they had experienced previous treatment failure (chemotherapy and/or radiation) for incompletely resected or unresectable low-grade glioma (LGG). Vinblastine (6 mg/m(2)) was administered weekly for 1 year unless unacceptable toxicity or progression (confirmed on two consecutive imaging studies) occurred. RESULTS Fifty-one patients (age range, 1.4 to 18.2 years; median age, 7.2 years) were prospectively enrolled onto this phase II study. Fifty patients had previously received at least one prior regimen of chemotherapy, and 10 patients had previously received radiation treatment. Fifty patients were evaluable for response; 18 patients (36%) had a complete, partial, or minor response, and 31 patients completed 1 year of treatment. At a median follow-up of 67 months, 23 patients had not experienced progression; three patients have died. Five-year overall survival was 93.2% ± 3.8%, and 5-year progression-free survival was 42.3% ± 7.2%. Toxicity was manageable and mostly hematologic, although a few patients needed transfusions. CONCLUSION Weekly vinblastine seems to be a reasonable alternative to radiation for pediatric patients with LGG who have experienced treatment failure with first-line chemotherapy. The 5-year progression-free survival observed in this phase II trial is comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation.