Sanjay P. Prabhu

Metabolic imaging of mild traumatic brain injury

Traumatic brain injury results in a metabolic cascade of changes that occur at the molecular level, invisible to conventional imaging methods such as computed tomography or magnetic resonance imaging. Non-invasive metabolic imaging tools such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance spectroscopy (MRS) are the ideal methods for providing insight to these changes by measuring regional cerebral blood flow, glucose metabolism, and brain metabolite concentrations, respectively, after mild traumatic brain injury (mTBI). The purpose of this review is to provide an overview of the different methodologies and provide an up-to-date summary of recent findings with SPECT, PET, and MRS technologies, specifically after mTBI, as defined by standardized criteria. Given that the different physiological and pathological responses are heterogeneous, efforts will be made to separate studies at different time points after injury (acute, subacute, and chronic stages) as well as to the different types of mTBI such sports-related head injury where repetitive head injuries are much more common and may present a unique signature.

Mechanical ventilation guided by electrical impedance tomography in experimental acute lung injury.

Objective:To utilize real-time electrical impedance tomography to guide lung protective ventilation in an animal model of acute respiratory distress syndrome. Design:Prospective animal study. Setting:Animal research center. Subjects:Twelve Yorkshire swine (15 kg). Interventions:Lung injury was induced with saline lavage and augmented using large tidal volumes. The control group (n = 6) was ventilated using ARDSnet guidelines, and the electrical impedance tomography–guided group (n = 6) was ventilated using guidance with real-time electrical impedance tomography lung imaging. Regional electrical impedance tomography–derived compliance was used to maximize the recruitment of dependent lung and minimize overdistension of nondependent lung areas. Tidal volume was 6 mL/kg in both groups. Computed tomography was performed in a subset of animals to define the anatomic correlates of electrical impedance tomography imaging (n = 5). Interleukin-8 was quantified in serum and bronchoalveolar lavage samples. Sections of dependent and nondependent regions of the lung were fixed in formalin for histopathologic analysis. Measurements and Main Results:Positive end-expiratory pressure levels were higher in the electrical impedance tomography–guided group (14.3 cm H2O vs. 8.6 cm H2O; p < 0.0001), whereas plateau pressures did not differ. Global respiratory system compliance was improved in the electrical impedance tomography–guided group (6.9 mL/cm H2O vs. 4.7 mL/cm H2O; p = 0.013). Regional electrical impedance tomography–derived compliance of the most dependent lung region was increased in the electrical impedance tomography group (1.78 mL/cm H2O vs. 0.99 mL/cm H2O; p = 0.001). Pao2/FIO2 ratio was higher and oxygenation index was lower in the electrical impedance tomography–guided group (Pao2/FIO2: 388 mm Hg vs. 113 mm Hg, p < 0.0001; oxygentation index, 6.4 vs. 15.7; p = 0.02) (all averages over the 6-hr time course). The presence of hyaline membranes (HM) and airway fibrin (AF) was significantly reduced in the electrical impedance tomography–guided group (HMEIT 42% samples vs. HMCONTROL 67% samples, p < 0.01; AFEIT 75% samples vs. AFCONTROL 100% samples, p < 0.01). Interleukin-8 level (bronchoalveolar lavage) did not differ between the groups. The upper and lower 95% limits of agreement between electrical impedance tomography and computed tomography were ± 16%. Conclusions:Electrical impedance tomography–guided ventilation resulted in improved respiratory mechanics, improved gas exchange, and reduced histologic evidence of ventilator-induced lung injury in an animal model. This is the first prospective use of electrical impedance tomography–derived variables to improve outcomes in the setting of acute lung injury.

Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex.

RATIONALE AND OBJECTIVES Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse neurologic outcome remains unclear. The aim of this study was to investigate the hypothesis that disordered white matter and abnormal neural connectivity are associated with adverse neurologic outcomes. MATERIALS AND METHODS Structural and diffusion magnetic resonance imaging was carried out in 40 subjects with TSC (age range, 0.5-25 years; mean age, 7.2 years; median age, 5 years), 12 of whom had autism spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the corpus callosum was used to define a three-dimensional volume of interest. Regional averages of four diffusion scalar parameters of the callosal projections were calculated for each subject. These were the average fractional anisotropy (AFA) and the average mean, radial, and axial diffusivity. RESULTS Subjects with TSC had significantly lower AFA and higher average mean, radial, and axial diffusivity values compared to controls. Subjects with TSC and ASD had significantly lower AFA values compared to those without ASD and compared to controls. Subjects with TSC without ASD had similar AFA values compared to controls. CONCLUSION Diffusion tensor scalar parameters provided measures of properties of the three-dimensional callosal projections. In TSC, changes in these parameters may reflect microstructural changes in myelination, axonal integrity, or extracellular environment. Alterations in white matter microstructural properties were associated with TSC, and larger changes were associated with TSC and ASD, thus establishing a relationship between altered white matter microstructural integrity and brain function.

Impaired Language Pathways in Tuberous Sclerosis Complex Patients with Autism Spectrum Disorders

The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential.

Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep

Purpose:  Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS.

The role of neuroimaging in sport-related concussion

This article describes some of the newer techniques that are being used in the clinical assessment of patients following mild to moderate TBI, addresses their use in the acute setting, and explores their potential role in long-term follow-up. Also addressed are the challenges faced before some of these newer techniques can be incorporated into routine clinical management. Large studies are needed with a special emphasis on the effects of repeated head trauma in the young athlete. This is especially relevant where conventional imaging does not demonstrate a macroscopic abnormality. The emphasis has to shift from identifying structural abnormalities on imaging studies to understanding the functional changes in the brain that may explain the long-term neuropsychological effects of concussion and mTBI.

Early thalamic lesions in patients with sleep-potentiated epileptiform activity

Objective: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). Methods: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. Results: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). Conclusions: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.

Acute Periorbital Infections: Who Needs Emergent Imaging?

OBJECTIVES: Computed tomography (CT) is used often in the evaluation of orbital infections to identify children who are most likely to benefit from surgical intervention. Our objective was to identify predictors for intraorbital or intracranial abscess among children who present with signs or symptoms of periorbital infection. These predictors could be used to better target patients for emergent CT. METHODS: This was a retrospective cohort study of all patients admitted to an urban pediatric tertiary care emergency department between 1995 and 2008. We included otherwise healthy patients with suspected acute clinical periorbital or orbital cellulitis without a history of craniofacial surgery, trauma, or external source of infection. Immunocompromised patients and patients with noninfectious causes of periorbital swelling were excluded. Variables analyzed included age, duration of symptoms, highest recorded temperature, previous antibiotic therapy, physical examination findings, laboratory results, and interpretation of imaging. CT scans of the orbit were reread by a neuroradiologist. RESULTS: Nine hundred eighteen patients were included; 298 underwent a CT scan, and of those, 111 were shown to have an abscess. Although proptosis, pain with external ocular movement, and ophthalmoplegia were associated with presence of an abscess, 56 (50.5%) patients with abscess did not experience these symptoms. Other variables associated with the presence of an abscess in multivariate analysis were a peripheral blood neutrophil count greater than 10 000/μL, absence of infectious conjunctivitis, periorbital edema, age greater than 3 years, and previous antibiotic therapy (P < .05 for all). Our recursive partitioning model identified all high-risk (44%) patients as well as a low-risk (0.4%–2%) group (Rsq = 0.27). CONCLUSIONS: We confirmed that patients with proptosis and/or pain or limitation of extraocular movements are at high risk for intraorbital abscess, yet many do not have these predictors. Other features can identify patients who do not have such obvious predictors but do have significant risk of disease. A recursive partitioning model is presented.

Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND)

To develop a statistical model for the tridimensional diffusion MRI signal at each voxel that describes the signal arising from each tissue compartment in each voxel.

Automated delineation of white matter fiber tracts with a multiple region-of-interest approach.

White matter fiber bundles of the brain can be delineated by tractography utilizing multiple regions-of-interest (MROI) defined by anatomical landmarks. These MROI can be used to specify regions in which to seed, select, or reject tractography fibers. Manual identification of anatomical MROI enables the delineation of white matter fiber bundles, but requires considerable training to develop expertise, considerable time to carry out and suffers from unwanted inter- and intra-rater variability. In a study of 20 healthy volunteers, we compared three methodologies for automated delineation of the white matter fiber bundles. Using these methodologies, fiber bundle MROI for each volunteer were automatically generated. We assessed three strategies for inferring the automatic MROI utilizing nonrigid alignment of reference images and projection of template MROI. We assessed the bundle delineation error associated with alignment utilizing T1-weighted MRI, fractional anisotropy images, and full tensor images. We confirmed the smallest delineation error was achieved using the full tensor images. We then assessed three projection strategies for automatic determination of MROI in each volunteer. Quantitative comparisons were made using the root-mean-squared error observed between streamline density images constructed from fiber bundles identified automatically and by manually drawn MROI in the same subjects. We demonstrate that a multiple template consensus label fusion algorithm generated fiber bundles most consistent with the manual reference standard.