Application of Quantitative Autoradiographic Measurements in Experimental Brain Tumor Models

Blasberg, Ronald G.; Groothuis, Dennis R.; Molnár, Péter

doi:10.1055/s-2008-1063898

Cited by 114 publications

(30 citation statements)

References 2 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Arterial pressure was monitored continuously via one femoral artery catheter. The other femoral artery catheter was cut to a total length of 8 cm and was connected to the ipsilateral venous catheter with a short (<I cm) length of silicon rubber tubing (internal diameter, 1.2 mm, LKB Instruments, Inc., Rockville, MD) (2). Just before the administration of isotope, 0.1 cc arterial blood was removed for determination of arterial gas tensions (Radiometer BM 53 MK2 Blood Micro System, Copenhagen, Denmark).…”

Section: Methodsmentioning

confidence: 99%

Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

et al. 1982

View full text Add to dashboard Cite

SummaryThe newborn beagle pup serves as a model for neonatal intraventricular hemorrhage (IVH). Fluctuations in germinal matrix blood flow are felt to play a major role in the pathogenesis of IVH. We studied regional cerebral blood flow in awake newborn beagle pups utilizing [14CI-iodoantipyrine as a blood flow indicator and quantitative autoradiography. The equilibrium [tissue]:[bloodl partition coefficient for iodoantipyrine was 1.13 + .06 for grey matter.Blood flow was calculated for cerebral cortex (frontal = 59 + 9 m1/100 &in), 14 subcortical nuclear structures (e.g., caudate = 45 + 6 m1/100 g/min), 3 white matter structures (centrum semiovale = 7 + 1 m1/100 g/min), and germinal matrix (7 + 1 m1/100 g/ min) (mean + S.E.).We conclude that under normal physiologic conditions the germinal matrix receives relatively low blood flow. This information can be used for comparison with germinal matrix blood flow during adverse experimental conditions. Speculation wLow baseline blood flow may place the germinal matrix at risk for ischemic injury during hypoxic or hypotensive stress. This ischemic injury may be a critical step in the pathogenesis of intraventricular hemorrhage, either by disrupting vascular integrity or by producing a disproportionate increase in germinal matrix blood flow (luxury perfusion) after reestablishment of normoxemia and normotension.Increasing attention is being focused on the regulation of cerebral blood flow (CBF) in newborn infants. The pathophysiology of both perinatal asphyxia and neonatal intraventricular hemorrhage have been linked to fluctuations in CBF (25). Although quantitative studies of CBF in newborn infants have been performed (22,24,29, 35), these results are limited by the poor spatial resolution of the techniques. Recent advances have made it possible to accurately measure blood flow to small brain regions in unanesthetized animals (1 8,19,30). We set out to study the regulation of regional blood flow (rCBF) in newborn animals. We utilized the beagle puppy as our experimental animal because the newborn beagle has recently been established as an animal model for neonatal intraventricular hemorrhage (8,9). In this report, we present in detail our methods and rCBF values for normal, unanesthetized pups. MATERIALS AND METHODSRegional cerebral blood flow (rCBF) was studied in newborn (12-48 h old) purebred beagle pups (Laboratory Research Enterprises, Inc., Kalamazoo, MI) by the methods of Sakurada et al.(30). The pups were lightly anesthetized with nitrous oxide and halothane. Polyethylene catheters filled with 1.0 international units (IU) Na heparin per 1.0 cc 0.9% NaCl were inserted bilaterally into the femoral arteries and veins via skin incisions. The wounds were infiltrated with 2% lidocaine jelly (Astra Pharmaceutical Products, Worcester, MA) and the hind quarters of the animal wrapped in a cotton stocking and fast-setting plaster bandage (Johnson and Johnson Co, New Brunswick, NJ). The plaster cast was secured to a lead brick. The animals were able to move their head and...

show abstract

Section: Methodsmentioning

confidence: 99%

Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

et al. 1982

View full text Add to dashboard Cite

show abstract

“…DiChiro et al (1984) discussed this issue and the LC in relation to their studies on human brain tumors with PET. Citing autoradio graphic evidence of the independence of DG uptake and BBB disruption (Blasberg et al , 1981) in animal glioma models and their own clinical experience in humans, they concluded that BBB disruption is un likely to affect the model significantly. They also concluded that LC probably was not changing sig nificantly in their tumor patients who were not char acterized by transport-limited ischemic states.…”

Section: Patient Studiesmentioning

confidence: 99%

Effects of Temporal Sampling, Glucose Metabolic Rates, and Disruptions of the Blood—Brain Barrier on the FDG Model with and without a Vascular Compartment: Studies in Human Brain Tumors with PET

Hawkins

Phelps

Huang

1986

J Cereb Blood Flow Metab

181

View full text Add to dashboard Cite

Summary: The addition of a cerebral blood volume (CBV) compartment in the rI8FJ2-fluoro-2-deoxY-D-glu cose (FDG) model produces estimates of local CBV si multaneously with glucose metabolic rates when kinetic FDG studies are performed. We investigated the influ ence of this term upon CMRglc values in a series of brain tumor patients and found that significant overestimations of CMRglc are possible if the effect of CBV upon the model is ignored. The magnitude of this potential over estimation is directly related to the absolute value of CBV The [ 1 8 F]2-tluoro-2-deoxY-D-glucose (FDG) meth od for estimating CMRglc with positron emission tomography (PET) is now widely utilized in normal and pathologic states (Phelps et aI ., 1982). The model, originally developed for deoxyglucose (DG) by Sokoloff et al. (1977), was modified by Phelps et al. [C�(t)J. this contribution was not included in the original Sokoloff model or in the Phelps and Huang modification because at the time of imaging (40 min after injection in a routine study) it is small com pared with C� and cZt. Additionally, in animal (i.e., rat) autoradiographic studies, the potential impact of intravascular activity is less than with human in vivo PET studies because the cerebral blood volume (CBV) in the decapitated animal is very small. However, in kinetic PET studies, the fraction of total tissue activity [C�(t)] in the vascular com partment is very high initially and neglecting its contribution can cause significant errors in the es timation of the model rate constants and calculated value of CMRglc. Initial kinetic studies by Phelps et al. (1979a) and Huang et al. (1980) minimized this problem by selecting regions for analysis that were at the more superior levels of the brain and distant from high blood volume territories. The CBV of the brain tends to decrease from inferior to superior sections and from lateral to medial. The exception to this is in the infero-medial territory of the venous

show abstract

“…Blood-brain barrier disruption can alter the hexose transport system and allow passive diffusion of glucose and [ (Blasberg et al, 1981). Alternations in tumour […”

Section: mentioning

confidence: 99%

Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography:a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas

Brock¹,

Young²,

O'Reilly

et al. 2000

Br J Cancer

108

View full text Add to dashboard Cite

Summary Quantitation of metabolic changes in tumours may provide an objective measure of clinical and subclinical response to anticancer therapy. This pilot study assesses the value of quantitation of metabolic rate of glucose (MRGlu) measured in mmol min -1 ml -1 to assess early subclinical response to therapy in a relatively non-responsive tumour. Nine patients receiving the CRC Phase II study schedule of temozolomide were assessed with [ -2 over 5 days every 28 days. Tumour MRGlu was calculated and compared with objective response at 8 weeks. Pretreatment MRGlu was higher in responders than non-responders. The responding patient group had a greater than 25% reduction in MRGlu in regions of high focal tumour uptake (HFU). Whole tumour changes in MRGlu did not correlate with response. Percentage change in HFU standardized uptake value (SUV) did discriminate the responding from the non-responding patients, but not as well as with MRGlu. Large differences also occurred in the normal brain SUV following treatment. Thus, MRGlu appeared to be a more sensitive discriminator of response than the simplified static SUV analysis. Changes in MRGlu may reflect the degree of cell kill following chemotherapy and so may provide an objective, quantitative subclinical measure of response to therapy.

show abstract

Application of Quantitative Autoradiographic Measurements in Experimental Brain Tumor Models

Cited by 114 publications

References 2 publications

Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

Effects of Temporal Sampling, Glucose Metabolic Rates, and Disruptions of the Blood—Brain Barrier on the FDG Model with and without a Vascular Compartment: Studies in Human Brain Tumors with PET

Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography:a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas

Contact Info

Product

Resources

About