Quantitative Measurement of Blood—Brain Barrier Permeability Using Rubidium-82 and Positron Emission Tomography

Brooks, David J.; Beaney, R. P.; Lammertsma, Adriaan A.; Leenders, Klaus L.; Horlock, Peter; Kensett, M.J.; Marshall, John; Thomas, D. G. T.; Jones, Terry

doi:10.1038/jcbfm.1984.78

Cited by 89 publications

(35 citation statements)

References 34 publications

(20 reference statements)

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“…The compartmental analysis presented here, showing the time course of tracer concentration in the lesion in response to a bolus injection, is applicable to all imaging modalities, not specifically MRI. Measurements of various transfer and rate constants have been made using PET with [ 68Ga]EDTA (18)(19)(20) and *'Rb+ (21,22). Our transfer constant k is equal to the influx constant Ki used by Iannotti et al ( 1 9 ) and Pozzilli et al ( 2 0 ) , although our model includes reflux from the lesion back to the plasma.…”

Section: Discussionmentioning

confidence: 98%

Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts

Tofts

Kermode

1991

Magnetic Resonance in Med

1,342

1,236

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Leakage of Gd-DTPA through a defective blood-brain barrier is measured quantitatively using dynamic MRI scanning, in which repeated scans are made after a bolus injection. Image registration artifacts are minimized; a dose of 0.1 mM/kg and an IR sequence enable enhancement to be measured quantitatively. The triexponential enhancement curve is fitted to a theoretical model based on compartmental analysis. The transfer constant, or permeability surface area product per unit volume of tissue (k), and leakage space per unit volume of tissue (v1) are measured. Estimates for a quickly enhancing multiple sclerosis lesion are k = 0.050 min-1, v1 = 21%; for a slow one k = 0.013 min-1, v1 = 49%. This implies permeability in the range 4-17 x 10(-6) cm s-1, in broad agreement with other physiological methods. The method is noninvasive and can be used to make serial measurements in patients and in experimental animal models. The time course of pathological aspects of diseases with blood-brain barrier breakdown, such as multiple sclerosis, tumors, and infections (e.g., HIV) can be studied, along with their response to therapy. The measurements are of physiological variables and are therefore independent of imaging equipment and field.

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Section: Discussionmentioning

confidence: 98%

Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts

Tofts

Kermode

1991

Magnetic Resonance in Med

1,342

1,236

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“…It is interesting to note that some of these studies were performed using generator-produced radionuclides including 68 Ga, 82 Rb and 62 Cu [38][39][40][41].…”

Section: Final Remarksmentioning

confidence: 99%

The new FDG brain revolution: the neurovascular unit and the default network

Sestini¹,

Castagnoli²,

Mansi³

2009

Eur J Nucl Med Mol Imaging

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"Our aim is, more than see new things, to see with new eyes what has already been seen" Baruch SpinozaThe first FDG brain revolutionThe first revolution was explosive. Using 18 F-fluorodeoxyglucose (FDG), it was possible to see and study the living brain in humans! Pioneers were top experts who provided different specialized expertise, but strictly cooperating between themselves [1]. Physicists, engineers and mathematicians were actively involved in producing the best hardware and software. The research on crystals, in identifying the most effective electronics, in defining accurate methods for attenuation and scatter correction and so on, was nevertheless limited by the relatively poor technology, with the main consideration being limited computer power. These developments stimulated a major interest in the brain. Satisfactory sensitivity and resolution, together with reliable solutions to the technical problems, were only achieved with dedicated cerebral PET scanners which had a field of view that permitted exclusive analysis of the brain.Basic scientists had the possibility of realizing a scientific dream: the transfer of data on cerebral glucose metabolism acquired in animals by quantitative autoradiography to humans. Another issue in the original FDG PET research was to consider mandatory absolute quantification. Thus arterial (or arterialized) sampling, to obtain data to be included in mathematical models, was routinely performed. However, because the equations included nonmeasurable parameters, the presence of a lumped constant affected absolute measurement in an individual [2][3][4]. PET teams included (and were directed by) clinical experts including not only nuclear physicians, but also other professionals such as neuroradiologists, neurologists and psychiatrists, who frequently cooperated with psychologists, anatomists and physiologists.Because of the unsatisfactory spatial resolution and the negative influence of the partial volume effect, in presence of glucose uptake in the normal brain, only a low lesion/background ratio was achievable, except for hot spots, i.e. the presence of focal areas of increased uptake determined by physiological and/or pathological causes. Therefore, the use of FDG as a positive indicator was restricted in the first studies and in the search for hot spots, many studies involved physiological stimulation tests (closed/open eyes, auditory system, etc.) in normal subjects [5,6]. Similarly, major interest in pathological analysis was directed to the evaluation of brain tumours, starting from Warburg's hypothesis of higher FDG uptake in malignant lesions with respect to benign ones [7]. With further clinical experience, in the analysis of patients with epilepsy, a higher sensitivity was clearly demonstrated during the ictal phase, the focus being seen as a hot spot, with respect to the interictal period when the lesion was not easily detectable, being an area with a slightly reduced overall FDG uptake [8,9]. Discrepant results in epilepsy clearly demonstrate how, in the absenc...

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“…Early measurements of global perfusion in multiple sclerosis using radioactive 133 Xe [31], positron emission tomography (PET) [32], or single photon emission computed tomography (SPECT) techniques [33] suffered from a very low spatial resolution. Findings of a generally lower perfusion in MS patients compared to healthy individuals were contradicted by the demonstration of increased perfusion during the time of acute inflammation in an animal model of MS [34].…”

Section: Cerebral Perfusion Changes Precede Blood-brain Barrier Breakmentioning

confidence: 99%

Cerebral blood perfusion changes in multiple sclerosis

Wuerfel

Paul

Zipp

2007

Journal of the Neurological Sciences

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| The proximity of immune cell aggregations to the vasculature is a hallmark of multiple sclerosis. Furthermore, it is widely accepted that inflammation is able to modulate the microcirculation. Until recently, the detection of cerebral blood perfusion changes was technically challenging, and perfusion studies in multiple sclerosis patients yielded contradictory results. However, new developments in fast magnetic resonance imaging have enabled us to image the cerebral hemodynamics based on the dynamic tracking of a bolus of paramagnetic contrast agents (dynamic susceptibility contrast). This review discusses the technical principles, possible pitfalls, and potential for absolute quantification of cerebral blood volume and flow in a clinical setting. It also outlines recent findings on inflammation associated perfusion changes, which are inseparable from pathological considerations in multiple sclerosis.

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Quantitative Measurement of Blood—Brain Barrier Permeability Using Rubidium-82 and Positron Emission Tomography

Cited by 89 publications

References 34 publications

Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts

Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts

The new FDG brain revolution: the neurovascular unit and the default network

Cerebral blood perfusion changes in multiple sclerosis

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