A New Tool to Assess Brain Vascular Health

March 9, 2015
Sergio Fantini, PhD

Noninvasive measurements of cerebral hemodynamics and oxygenation can have a significant impact on the assessment of cerebrovascular conditions and can monitor the effects of clinical procedures on brain circulation.

Coherent hemodynamics spectroscopy (CHS), a new technique to assess cerebrovascular health, measures the cerebral hemodynamic response to controlled perturbations in the systemic mean arterial blood pressure (ABP).

Noninvasive measurements of cerebral hemodynamics and oxygenation can have a significant impact on the assessment of cerebrovascular conditions, such as subarachnoid hemorrhage, traumatic brain injury, ischemic stroke, and vascular dementia. These measurements also can monitor the effects on brain circulation of clinical procedures, such as hemodialysis, cardiopulmonary bypass, and general anesthesia.

Near-infrared Spectroscopy Technique to Illuminate the Brain

One technique for noninvasive measurements of cerebral perfusion and oxygenation is near-infrared spectroscopy (NIRS), which relies on the relatively low optical absorption of biological tissues in the red to near-infrared spectral region (say, at wavelengths between 650 and 1000 nm). At these wavelengths, light is transmitted through thick tissues, as one can verify by shining a white torchlight on the palm of a hand and seeing the red light transmitted through the back of the hand.

Light at shorter wavelengths is absorbed in the tissue, but red/near-infrared light is transmitted through centimeters of tissue. The levels of transmitted light carry valuable information about the concentration and oxygen saturation of hemoglobin in perfused tissues. Even though red/near-infrared light is weakly absorbed in tissue, it is highly scattered by cells and cellular organelles, resulting in the diffuse illumination of tissue (a laser pointer directed to a finger illuminates the entire finger by light diffusion).

However, as sunlight penetrates through the cloud layer on a cloudy day, so does near-infrared light penetrate through the intact scalp and skull layers to illuminate the cerebral cortex. Some of the light that illuminates the brain cortex makes it back through the skull and scalp and can be detected in a noninvasive fashion. This is the basic approach of the diffuse optical methods of NIRS, to sense the brain noninvasively by placing a set of illumination and collection optical fibers on the subject’s scalp.1

The New Technique of Coherent Hemodynamics Spectroscopy

NIRS provides measures of the concentration and oxygen saturation of hemoglobin in the cerebral microvasculature, thus providing information about cerebral perfusion and oxygenation. The new technique of CHS, developed at Tufts University,2 enriches the information content extracted from NIRS data to yield dynamic measures of cerebral blood volume, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen.

The name of this new technique signifies frequency-resolved measurements (a spectroscopy approach) of cerebral hemodynamics that are coherent (ie, feature a well-defined and stable phase). A most effective way to achieve coherent hemodynamics is to drive them with periodic perturbations to the systemic ABP.

There are periodic oscillations in the ABP that are naturally occurring at the heart rate and respiratory rate, because the heart beat and cyclic changes in intrathoracic pressure due to respiration modulate the mean arterial pressure (MAP). Paced breathing or external manipulations (eg, inflating and deflating pneumatic thigh cuffs placed around the subject’s limbs) achieve regular cyclic perturbations to the systemic MAP that induce coherent hemodynamics in tissues.

Information About Hemodynamic Quantities

The conceptual approach of CHS is thereby to induce controlled perturbations in the systemic MAP and measure, with NIRS or other hemodynamic-based techniques, the resulting local hemodynamics in brain tissue. The local hemodynamic response to the systemic MAP changes contains information about a number of baseline and dynamic physiological quantities, including microvascular blood flow, cerebrovascular reactivity, and dynamic cerebral autoregulation. To extract quantitative information about these hemodynamic quantities, we use a novel mathematical model that relates NIRS signals to the underlying dynamic changes of blood volume, flow, and oxygen consumption.2

Initial applications of CHS have demonstrated its applicability in a clinical setting, the hemodialysis unit, where we found a reduced CBF in patients undergoing hemodialysis compared with a healthy control group.3 We also have used CHS to measure dynamic cerebral autoregulation (the critical ability of the healthy brain to regulate CBF in response to perturbations to cerebral perfusion pressure) in a cohort of healthy subjects during regular breathing (normal autoregulation) and a hypocapnic condition achieved with hyperventilation (which is known to enhance autoregulation).4

Broader Applicability of CHS

Currently, CHS is being further developed to achieve brain mapping capabilities and to demonstrate its potential in a number of clinical areas aimed at the assessment of brain vascular health. Its basic approach of inducing controlled perturbations to the systemic ABP and measuring the local hemodynamic response can be applied to other tissues as well, for example, the human breast, for detecting, characterizing, and monitoring the abnormal blood perfusion associated with breast cancer.

Other techniques, besides NIRS, can measure coherent tissue hemodynamics, for example, MRI methods aimed at blood perfusion or blood oxygenation. These techniques also can implement the basic principles of CHS.

References:

1. Ferrari M, Quaresima V. A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application. Neuroimage.2012;63:921-935.

2. Fantini S. Dynamic model for the tissue concentration and oxygen saturation of hemoglobin in relation to blood volume, flow velocity, and oxygen consumption: implications for functional neuroimaging and coherent hemodynamics spectroscopy (CHS). Neuroimage. 2014;85(Pt 1):202-221.

3. Pierro ML, Kainerstorfer JM, Civiletto A, et al. Reduced speed of microvascular blood flow in hemodialysis patients versus healthy controls: a coherent hemodynamics spectroscopy study. J Biomed Opt. 2014;19:026005. doi: 10.1117/1.JBO.19.2.026005.

4. Kainerstorfer JM, Sassaroli A, Tgavalekos KT, Fantini S. Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy. J Cereb Blood Flow Metab.2015 Feb 11. doi: 10.1038/jcbfm.2015.5. [Epub ahead of print]