Rudi Schulte Research Institute

Santa Barbara, CA, United States

Rudi Schulte Research Institute

Santa Barbara, CA, United States
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Panigrahy A.,University of Pittsburgh | Moore K.R.,Primary Childrens Medical Center | Gonzalez-Gomez I.,All Childrens Hospital | Bluml S.,Rudi Schulte Research Institute
Neuroradiology | Year: 2015

Introduction: The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Methods: Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Results: Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Conclusion: Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. © 2015, Springer-Verlag Berlin Heidelberg.

Chen H.J.,University of California at Los Angeles | Panigrahy A.,Childrens Hospital Los Angeles | Panigrahy A.,University of Pittsburgh | Dhall G.,Childrens Hospital Los Angeles | 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.

Wisnowski J.L.,Childrens Hospital Los Angeles | Wisnowski J.L.,University of Pittsburgh | Schmithorst V.J.,University of Pittsburgh | Rosser T.,Childrens Hospital Los Angeles | And 8 more authors.
Neuroradiology | Year: 2014

Introduction: Punctate white matter lesions (pWMLs) and diffuse excessive high signal intensity (DEHSI) are commonly observed signal abnormalities on MRI scans of high-risk preterm infants near term-equivalent age. To establish whether these features are indicative abnormalities in axonal development or astroglia, we compared pWMLs and DEHSI to markers of axons and astrogliosis, derived from magnetic resonance spectroscopy (MRS).Methods: Data from 108 preterm infants (gestational age at birth 31.0 weeks ± 4.3; age at scan 41.2 weeks ± 6.0) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses were used to test the effects of pWMLs and DEHSI on N-acetyl-aspartate (NAA) and myoinositol concentrations, respectively.Results: Across the full sample, pWMLs were associated with a reduction in NAA whereas moderate to severe DEHSI altered the normal age-dependent changes in myoinositol such that myoinositol levels were lower at younger ages with no change during the perinatal period. Subgroup analyses indicated that the above associations were driven by the subgroup of neonates with both pWMLs and moderate to severe DEHSI.Conclusion: Overall, these findings suggest that pWMLs in conjunction with moderate/severe DEHSI may signify a population of infants at risk for long-term adverse neurodevelopmental outcome due to white matter injury and associated axonopathy. The loss of normal age-associated changes in myoinositol further suggests disrupted astroglial function and/or osmotic dysregulation. © 2014, Springer-Verlag Berlin Heidelberg.

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 4 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.

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.

Bluml S.,Childrens Hospital Los Angeles | Bluml S.,Rudi Schulte Research Institute | Panigrahy A.,Childrens Hospital Los Angeles | Panigrahy A.,Childrens Hospital of Pittsburgh of UPMC | And 7 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.

Yeom K.W.,Stanford University | Lober R.M.,Stanford University | Nelson M.D.,Childrens Hospital Los Angeles | Panigrahy A.,University of Pittsburg | And 2 more authors.
Journal of Neuro-Oncology | Year: 2015

Citrate, a tricarboxylic acid cycle intermediate, is present in high concentrations in pediatric diffuse intrinsic pontine gliomas (DIPG). Since citrate increases during hypoxia in animal studies, we hypothesized that it accumulates in DIPG when hypoperfused. Relative tumor blood volumes (rTBV) were determined, using dynamic susceptibility contrast-enhanced magnetic resonance imaging, in twelve children [median age 8.2 (range 3.2–14.5) years] with DIPG and compared to citrate concentrations measured with in vivo proton magnetic resonance spectroscopy (1H MRS). Tissue perfusion and metabolite concentration were assessed at initial presentation and over the clinical course, yielding 36 and 46 perfusion and MR spectroscopy datasets, respectively. At presentation, DIPG blood volume was 60 ± 27 % of that measured for normal cerebellum. Citrate, which is not detectable in normal brain tissue, was present in DIPG at concentrations of 3.81 ± 1.44 mmol/kg tissue. Over the course of the disease and treatment, rTBV increased and citrate decreased (both p < 0.05) with an inverse correlation (p = 0.028). Citrate accumulation is associated with tissue hypoperfusion in DIPG. © 2015, Springer Science+Business Media New York.

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.

Sailasuta N.,Huntington Memorial Research Institute | Abulseoud O.,University of Southern California | Hernandez M.,University of Southern California | Hernandez M.,Rudi Schulte Research Institute | And 3 more authors.
Substance Abuse: Research and Treatment | Year: 2010

Introduction: Chronic methamphetamine use results in persistent neuropsychological deficits in abstinent methamphetamine dependent (AMD) subjects. We examined the hypothesis that elevated concentration of cerebral glutamate (Glu), an excitatory neurotransmitter and neurotoxin, occurs in human AMD. Materials and Methods: We examined 40 subjects, 18 of whom were AMD, abstinent more than 3 weeks and 22 were age matched controls. A Structured Clinical Interview was applied to exclude AMD with comorbid depression. We used TE-Averaged technique of MRS to uniquely identify and quantify the glutamate resonance at 2.35 ppm on a 3T clinical MR scanner. Statistics, including Bonferroni correction for multiple MRS variables were applied. Results: Glu was significantly higher in frontal white matter of AMD (+19%, P = 0.01) and N-acetylaspartate (NAA), an axonal marker, was lower (-14%, P = 0.004). No significant MRS abnormalities were detected in posterior gray matter. Significant correlations were observed between NAA and Glu (P = 0.002 for AMD and P = 0.06 for controls in the posterior gray matter and P = 0.01 for controls and not significant for AMD in the frontal white matter). Conclusion: Our results demonstrate a significant excess of glutamate in frontal white matter of AMD subjects and offer support for the hypothesis that methamphetamine abuse may exert its long-term neuro-toxicity via glutamate. © the author(s), publisher and licensee Libertas Academica Ltd.

Sailasuta N.,Huntington Memorial Research Institute | Abulseoud O.,University of Southern California | Harris K.C.,Huntington Memorial Research Institute | Ross B.D.,Huntington Memorial Research Institute | Ross B.D.,Rudi Schulte Research Institute
Journal of Cerebral Blood Flow and Metabolism | Year: 2010

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized 13C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P > 0.1). However, glial 13 C-bicarbonate production rate from [1- 13C] Cacetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 μmol/g per min (N5) versus controls 0.11 μmol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous 13 C MRS methods may determine cause and effect between glial failure and neuronal injury. © 2010 ISCBFM.

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