Methods of evaluating cerebrovascular reactivity using transcranial doppler

Inventors

Alwatban, Mohammed • Bashford, Gregory R.

Assignees

NuTech Ventures Inc

Abstract

Provided here are methods of detecting compromised cerebrovascular reactivity in a subject and treating such subject. The method includes acquiring transcranial Doppler signals and cardiac measurements from the subject following a breath-hold maneuver and recording a test set of CBFV measurements. A breath-hold acceleration index is calculated based on a linear regression correlation of temporal variations of the mean velocity across all cardiac cycles during the breath-hold maneuver. The presence of compromised cerebrovascular reactivity in the subject is detected in response to variations in the breath-hold acceleration index of the subject as compared to a healthy individual performing breath-hold maneuver under similar conditions. If the subject has compromised cerebrovascular reactivity, a therapeutically effective compound is administered to the subject along with provision of behavioral modification regimen.

Core Innovation

The disclosure describes transcranial Doppler signals obtained during a breath-hold maneuver to evaluate compromised cerebrovascular reactivity (CVR). Cerebral blood flow velocity (CBFV) measurements are calculated from the transcranial Doppler signals, and cardiac measurements are acquired during the breath-hold maneuver including systolic velocity (Vs) and diastolic velocity (Vd) in each cardiac cycle. A mean velocity is calculated by averaging the CBFV measurements within each cardiac cycle, and the breath-hold acceleration index is calculated from a linear regression correlation of temporal variations of the mean velocity across all cardiac cycles during the breath-hold maneuver.

Compromised cerebrovascular reactivity is detected by comparing the breath-hold acceleration index of the subject to a breath-hold acceleration index of a healthy individual performing the breath-hold maneuver under similar conditions. The disclosure specifies detection when the breath-hold acceleration index of the subject is more than one standard deviation less than the breath-hold acceleration index of the healthy individual, with an additional Alzheimer’s disease threshold described as more than two standard deviations below the healthy individual in the disclosure summary.

The disclosure further provides treatment in response to detection, including administering a therapeutically effective compound or providing a behavioral modification regimen. For detecting preclinical Alzheimer’s disease, a method is described that administering a therapeutically effective compound to the subject detected of having preclinical Alzheimer’s disease, and for treating compromised cerebrovascular reactivity, a method is described that administering a therapeutically effective compound along with providing a behavioral modification regimen.

Claims Coverage

The provided material contains three independent claims: clm-00001, clm-00012, and clm-00018. Across these independent claims, the same core inventive detection framework is used—transcranial Doppler breath-hold signals, cardiac-cycle mean velocity, and a breath-hold acceleration index derived from linear regression of temporal variations—followed by treatment triggered by the detected condition.

The independent claims share the use of a breath-hold acceleration index derived from linear regression of temporal variations in cardiac-cycle mean CBFV during a breath-hold maneuver, detect impairment by a standard deviation comparison to a healthy reference under similar conditions, and then provide treatment triggered by the detected compromised CVR or preclinical Alzheimer’s disease.

Stated Advantages

Documented Applications