title: Citrate concentrations increase with hypoperfusion in pediatric diffuse intrinsic pontine glioma.
abstract: 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 ((1)H 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.
authors: Department of Radiology, Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA.
authors: Kristen W
authors: KW
authors: Yeom
authors: Robert M
authors: RM
authors: Lober
authors: Marvin D
authors: MD
authors: Nelson
authors: Ashok
authors: A
authors: Panigrahy
authors: Stefan
authors: S
authors: Blüml
mesh_terms: D000293:Adolescent; D001810:Blood Volume; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D020295:Brain Stem Neoplasms / Q000503:physiopathology* / Q000628:therapy; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D002951:Citrates / Q000378:metabolism*; D003287:Contrast Media; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D016019:Survival Analysis
chemical_list: D002951:Citrates; D003287:Contrast Media