CP #10: Blood Pressure, Cerebral Perfusion and Cognitive Performance in Hypertension

Blood Pressure, Cerebral Perfusion and Cognitive Performance in Hypertension

Significance:

Hypertension (HTN) or high blood pressure is one of the leading health issues Americans face today. More than half of the US population over the age of 60 suffers from high blood pressure [1]. While hypertension can lead to heart disease and kidney damage, there is also evidence suggesting that high blood pressure may lead to brain damage, e.g. via stroke and Alzheimer’s disease (AD). Not only does HTN cause vascular remodeling, but it is considered a major cause of small vessel disease leading to infarctions and white matter lesions. There is also a growing body of evidence that HTN can elevate the biochemical and neuropathological abnormalities that occur in AD, such as increasing the production of amyloids [2] and exacerbating neurofilbrillary tangles [3]. Over time, HTN increases the risk of cognitive decline [4] and contributes to brain atrophy [5]. At the same time, HTN may increase the brain’s vulnerability to hypoperfusion. Studies have shown that cerebral regulation is better adapted to compensate for sudden increases rather than decreases in BP [6]. Deficient autoregulation in HTN may make cerebral blood flow (CBF) more dependent on perfusion pressure, increasing thresholds for mean arterial pressure at which CBF is safely maintained.

It is our central hypothesis (see Figure 1) that a unique BP value exists that maximizes the probability of CBF preservation within different subject groups with different baseline BP and different burdens of white matter lesions (WML).

Aims:

In this project, we will use imaging measures (cerebral perfusion with arterial spin labelling (ASL), MR spectroscopy (MRS) and structural brain imaging) to provide insight into the complex relationship between BP, CBF, metabolic composition, brain structure and cognitive outcome in subjects with HTN presenting with different WML burdens.

Approach:

A longitudinal 24-month study will be performed with 180 cognitively normal hypertensive elderly subjects (90 without WML and 90 with WML) along with 50 normotensive controls. On initial workup, subjects will undergo a comprehensive medical and spectroscopic/imaging evaluation (whole brain NAA with MRS, TrueFISP ASL, and structural imaging). With this data, we will analyze the mean arterial pressure (MAP) relationship with CBF in the three groups to determine the optimal BP and hemodynamic metrics for preservation of cognition for each group. Subjects’ BP will be lowered to the optimal value at the 12-month follow up. To examine whether the optimal baseline BP has an effect on brain volumes and brain tissue metabolic integrity, the subjects will undergo another comprehensive medical and imaging evaluation at the 24-month mark.

Push-Pull Relationship with TR&D Projects 1, 2, &3:

TR&D#1: Since some of the MR techniques employed in this project require prolonged acquisition, we expect to benefit from as well as foster development of robust rapid imaging techniques in TR&D #1. It has been demonstrated, for example, that spectroscopic acquisitions can benefit significantly from parallel imaging reconstruction methods enabling reduced scan time [7,8].  Combinations with compressed sensing and comprehensive volumetric acquisition approaches are expected to yield further benefits. TrueFISP ASL provides a high resolution and susceptibility-artifact-free picture of perfusion. However its current acquisition time (2 min per slice) limits the achievable brain coverage. We will deploy the developments in acquisition and reconstruction from TR&D #1 to reduce scan time per slice, with the ultimate aim of enabling full brain coverage. 

TR&D#2: Based on promising experience by BTRC staff with high-resolution T1-weighted images enabled by parallel transmission [9] and high-SNR spectroscopy [10], we will extend our current 3T study to 7T, in order to gain further insight into hippocampal, cerebellar and white matter anatomy that is crucial for our project. 

TR&D#3:  The availability of a scanner with simultaneous MR and PET acquisition will enable us to expand our project in collaboration with the TR&D #3 research team. Specifically, following a recent report de­scribing feasibility of True FISP ASL on an MR-PET scanner [11], we will explore simultaneous acquisition of perfusion scans and oxygen metabolic rates.  Additional applications we envision for the future include cross-validation of flow measurements using TrueFISP ASL and PET, and use of new endothelial-specific imaging agents [12] for simultaneous visualization of parenchymal perfusion and intracranial atherosclerotic lesions in vessels.

Principal Investigator: 

Sponsors

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Philanthropic Support

We gratefully acknowledge generous support for radiology research at NYU Langone Medical Center from:
 
• The Big George Foundation
• Raymond and Beverly Sackler
• Bernard and Irene Schwartz

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