System and Method For Blood Brain Permeability Imaging (BBPI) Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging

Description:
The blood-brain barrier (BBB) plays a critical role in both normal function and pathological states of the brain. While disruption of the BBB can be a hallmark of disease activity, the BBB also serves as a barrier to drug delivery. Thus, imaging the BBB has innumerable applications. Previous attempts to image the BBB have not been sensitive enough to detect subtle changes and are either very time consuming (DCE), or not quantitative (post-contrast T1).

Blood Brain Permeability Imaging (BBPI) represents a breakthrough in imaging the integrity of the BBB. The method uses dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) which is a commonly acquired sequence in the clinical care of patients. A DSC acquisition typically takes 1-2 minutes of scanner time and is commonly processed to produce maps that reflect blood flow metrics. However, it has long been known that, in the setting of BBB disruption, the recorded signal from a DSC acquisition also reflects leakage of contrast agent through the BBB. Separating the signal into flow and leakage had been challenging until the advent of BBPI.

BBPI can be generated from any DSC sequence, either in real-time when the images are acquired, or after the fact in a retrospective manner. Using this method, brain properties such as reversible BBB disruption with ischemia, which had previously only been studied in animals, have now been demonstrated in humans. Although originally designed to perform well in acute ischemic stroke, a situation where there are large variations in regional blood flow, it has also performed well in diseases with minor fluctuations in blood flow, such as Multiple Sclerosis. One of the biggest breakthroughs was the discovery that it could detect BBB disruption associated with vascular dementia, a signal change that is on an order of magnitude smaller than is seen with acute ischemic events. This technology has potential applications to almost any pathologic state associated with brain injury including intracranial hemorrhage, brain cancer, epilepsy, neuro-inflammatory conditions, and cognitive impairment/dementia. It could be used to identify/diagnose disease, monitor disease activity, measure response to therapy, and as an outcome measure for clinical trials.

Publications:
Arba F, Leigh R, Inzitari D, Warach SJ, Luby M, Lees KR. Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke. Neurology. 2017; 89 (21):2143-2150.

Butler J, Heidari P, Blayney S, Hitomi E, Luby M, Leigh R.  Blood-brain barrier integrity of stroke patients presenting in an extended time window.  BMC Neurology. 2020; 20:54.
 
Caunca MR, De Leon-Benedetti A, Latour L, Leigh R, Wright CB. Neuroimaging of Cerebral Small Vessel Disease and Age-Related Cognitive Changes. Front Aging Neurosci. 2019; 11:145.
 
Gupta N, Simpkins AN, Hitomi E, Dias C, Leigh R. White Matter Hyperintensity-Associated Blood-Brain Barrier Disruption and Vascular Risk Factors. J Stroke Cerebrovasc Dis. 2018; 27(2):466-471.

Leigh R, Jen SS, Varma DD, Hillis AE, Barker PB. Arrival Time Correction for Dynamic Susceptibility Contrast MR Permeability Imaging in Stroke Patients. PLoS ONE. 2012; 7(12):e52656.
 
Leigh R, Christensen S, Campbell BCV, Marks MP, Albers GW, Lansberg MG. Pretreatment blood–brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology. 2016; 87(3):263-269.
 
Nadareishvili Z, Simpkins AN, Hitomi E, Reyes D, Leigh R. Post-Stroke Blood-Brain Barrier Disruption and Poor Functional Outcome in Patients Receiving Thrombolytic Therapy. Cerebrovasc Dis. 2019; 47(3-4): 135-142.
 
Simpkins AN, Dias C, Leigh R. Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia. Stroke. 2016; 47(9):2405-8.
 
Naqvi I, Hitomi E, Leigh R. Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke. Brain Sci. 2019; 9(1).

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