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Shiroishi M.S.,Childrens Hospital Los Angeles | Jackson H.A.,Childrens Hospital Los Angeles | Nelson Jr. M.D.,Childrens Hospital Los Angeles | Bluml S.,Rudi Schulte Research Institute | Panigrahy A.,Childrens Hospital of Pittsburgh of UPMC
Pediatric Radiology | Year: 2010

Identification of abnormalities in the contralateral hemisphere in patients with hemimegalencephaly is critical in their management. In this report, we present a 5-day-old neonate with hemimegalencephaly who demonstrated an enlarged ipsilateral cerebral hemisphere and diffuse volume loss in the contralateral hemisphere on conventional MR imaging sequences. The ipsilateral frontal white matter demonstrated relatively increased NAA, fractional anistropy, and cerebral blood volume values compared to published normative data. In addition, the white matter of the contralateral hemisphere demonstrated elevated lactate and increased mean diffusivity compared to published normative data, supporting the abnormal conventional MR findings. Advanced MR neuroimaging techniques may help further confirm and characterize abnormalities in the smaller contralateral hemisphere in neonatal hemimegalencephaly. © Springer-Verlag 2010. Source

Chen H.J.,University of California at Los Angeles | Panigrahy A.,Childrens Hospital Los Angeles | Panigrahy A.,University of Pittsburgh | Dhall G.,Childrens Center for Cancer and Blood Diseases | And 4 more authors.
American Journal of Neuroradiology | Year: 2010

BACKGROUND AND PURPOSE: DIBSGs have the worst prognosis among pediatric brain tumors with no improvement of outcome for several decades. In this study, we determined whether diffusion imaging could improve patient stratification and our understanding of the impact of therapies. MATERIALS AND METHODS: Nine baseline and 24 follow-up DTI studies performed in 9 patients on a 1.5T clinical MR imaging scanner were reviewed. ADC and FA were measured for the whole lesion and at 5 anatomic levels: the rostral medulla, caudal pons, midpons, rostral pons, and caudal midbrain. Reference data were obtained from 8 controls with normal brain stem, 6 patients with medulloblastoma, and 7 patients with pilocytic astrocytoma. RESULTS: ADC was higher in untreated DIBSG than in normal brain stem and medulloblastoma (1.14 ± 0.18 [×10-3 mm2/s] versus 0.75 ± 0.06 and 0.56 ± 0.05, both P < .001). FA was lower in DIBSG than in normal brain stem (0.24 ± 0.04 versus 0.43 ± 0.02, P < .001) but was higher than that in pilocytic astrocytoma (0.17 ± 0.05, P < .05). Lower baseline ADC and higher FA correlated with a worse clinical course. Correlations were more significant at the caudal midbrain than in other regions. ADC decreased and FA increased after RT. Changes of FA after RT at the caudal midbrain correlated with event-free survival. CONCLUSIONS: Baseline ADC and FA of DIBSG revealed hypocellular tumors with extensive edema. Diffusion changes after therapy implied reduced edema but did not support a significant response to therapy. The significance of diffusion properties varied with anatomic locations, the caudal midbrain being particularly important. Source

Bluml S.,Childrens Hospital Los Angeles | Bluml S.,Rudi Schulte Research Institute | Wisnowski J.L.,Childrens Hospital Los Angeles | Wisnowski J.L.,University of Southern California | And 3 more authors.
PLoS ONE | Year: 2014

Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ≈340-370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury. © 2014 Blüml et al. Source

Bluml S.,Childrens Hospital Los Angeles | Bluml S.,Rudi Schulte Research Institute | Panigrahy A.,Childrens Hospital Los Angeles | Laskov M.,Childrens Center for Cancer and Blood Diseases | And 6 more authors.
Neuro-Oncology | Year: 2011

In vivo magnetic resonance spectroscopy (MRS) provides information about metabolite concentrations in tissue. Recently citrate was detected by MRS in subgroups of pediatric brain tumors. Citrate is an intermediate in the tricarboxylic acid (TCA) cycle and accumulates in tissue when the glycolytic rate exceeds the TCA cycle activity, a feature of malignant tumors. Currently, no practical indicators allow clinicians to predict risk for malignant progression of pediatric astrocytomas (World Health Organization [WHO] grade II). Medical records and citrate concentrations measured with in vivo MRS of 29 pediatric astrocytomas were reviewed. This included 6 patients with astrocytomas (WHO II) who had stable disease (indolent LGA) for >2 years, 7 with aggressive grade II astrocytomas (aggressive LGA), 13 with anaplastic astrocytomas (WHO III), and 3 with glioblastoma (WHO IV) with disease progression within 2 years. Citrate was observed in all patients with aggressive LGA, and the mean citrate concentration was significantly higher in this group than among those with indolent LGA (mean+standard deviation, 4.1 ±1.1 vs 0.6 ±0.8 mmol/kg; P <.0001). There was no consistent pattern for citrate in anaplastic astrocytoma and glioblastoma, with citrate prominent in some lesions whereas undetectable in others. It is unclear whether citrate accumulation occurred because of fundamental defects of citrate regulation or was secondary to altered physiological conditions. Nonetheless, prominent citrate identified a subgroup of pediatric grade II astrocytomas destined for aggressive behavior. Citrate was not specific for poor outcome because it was not detectable in all high-grade astrocytomas. In highgrade astrocytoma, tumors with prominent citrate may constitute a metabolic subclass. © The Author(s) 2011. Source

Bhattacharya P.,Huntington Memorial Research Institute | Chekmenev E.Y.,Huntington Memorial Research Institute | Chekmenev E.Y.,Rudi Schulte Research Institute | Reynolds W.F.,Sanford Burnham Institute for Medical Research | And 5 more authors.
NMR in Biomedicine | Year: 2011

MR techniques using hyperpolarized 13C have successfully produced examples of angiography and intermediary metabolic imaging, but, to date, no receptor imaging has been attempted. The goal of this study was to synthesize and evaluate a novel hyperpolarizable molecule, 2,2,3,3-tetrafluoropropyl 1- 13C-propionate-d 2,3,3 (TFPP), for the detection of atheromatous plaques in vivo. TFPP binds to lipid bilayers and its use in hyperpolarized MR could prove to be a major step towards receptor imaging. The precursor, 2,2,3,3-tetrafluoropropyl 1- 13C-acrylate-d 2,3,3 (TFPA), binds to 1,2-dimyristoylphosphatidylcholine lipid bilayers with a 1.6-ppm chemical shift in the 19F MR spectrum. This molecule was designed to be hyperpolarized through the addition of parahydrogen to the 13C-acrylate moiety by parahydrogen-induced polarization. TFPA was hyperpolarized to TFPP to an extent similar to that of the hydroxyethylacrylate to hydroxyethylpropionate transition: 17±4% for TFPP versus 20% for hydroxyethylpropionate; T 1 relaxation times (45±2s versus 55±2s) were comparable and the hyperpolarized properties of TFPP were characterized. Hydroxyethylacrylate, like TFPA, has a chemical structure with an acrylate moiety, but does not contain the lipid-binding tetrafluoropropyl functional group. Hyperpolarized TFPP binds to the lipid bilayer, appearing as a second, chemically shifted 13C hyperpolarized MR signal with a further reduction in the longitudinal relaxation time (T 1 = 21±1s). In aortas harvested from low-density lipoprotein receptor knock-out mice fed with a high-fat diet for 9months, and in which atheroma is deposited in the aorta and heart, TFPP showed greater binding to lipid on the intimal surface than in control mice fed a normal diet. When TFPP was hyperpolarized and administered in vivo to atheromatous mice in a pilot study, increased binding was observed on the endocardial surface of the intact heart compared with normally fed controls. Hyperpolarized TFPP has bio-sensing specificity for lipid, coupled with a 42 000-fold sensitivity gain in the MR signal at 4.7T. Binding of TFPP with lipids results in the formation of a characteristic second peak in MRS. TFPP therefore has the potential to act as an in vivo molecular probe for atheromatous plaque imaging and may serve as a model of receptor-targeted bio-imaging with enhanced MR sensitivity. © 2011 John Wiley & Sons, Ltd. Source

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