A Noninvasive Method for Monitoring Intracranial Pressure During Postural Changes.

Intracranial hypertension (IH) is an important cause of secondary brain injury, and its association with poor outcomes has been extensively demonstrated. Pathological intracranial hypertension is defined as a persistent rise in intracranial pressure (ICP) to above 20-25 mmHg, with symptoms such as headaches, loss of consciousness, seizures, and focal deficits, as well as ischemic damage. Therefore, monitoring of ICP is invaluable in the management of these symptoms. However, invasive measurements of ventricular pressure (requiring a surgical procedure) are considered the gold standard, thus limiting the practicality of ICP measurements. Vivonics, Inc., is developing a noninvasive optical device to assess ICP for use by emergency medical personnel, called IPASS: Intracranial Pressure Assessment and Screening System. IPASS uses four near-infrared sensors to measure hemodynamic oscillations at four different locations. Three sensors are used as reference signals and one sensor is used to detect cerebral blood volume oscillations. Pulse arrival delays between the measured cerebral blood volume oscillations and the blood volume oscillations measured at the three reference locations are calculated and correlated with estimated ICP changes, herein modulated by specific positional changes (in a head-down maneuver).

Reduced speed of microvascular blood flow in hemodialysis patients versus healthy controls: a coherent hemodynamics spectroscopy study.

We present a pilot clinical application of coherent hemodynamics spectroscopy (CHS), a technique to investigate cerebral hemodynamics at the microcirculatory level. CHS relies on frequency-resolved measurements of induced cerebral hemodynamic oscillations that are measured with near-infrared spectroscopy (NIRS) and analyzed with a hemodynamic model. We have used cyclic inflation (200 mmHg) and deflation of a pneumatic cuff placed around the subject's thigh at seven frequencies in the range of 0.03 to 0.17 Hz to generate CHS spectra and to obtain a set of physiological parameters that include the blood transit times in the cerebral microcirculation, the cutoff frequency for cerebral autoregulation, and blood volume ratios across the three different compartments. We have investigated five hemodialysis patients, during the hemodialysis procedure, and six healthy subjects. We have found that the blood transit time in the cerebral microcirculation is significantly longer in hemodialysis patients with respect to healthy subjects. No significant differences were observed between the two groups in terms of autoregulation efficiency and blood volume ratios. The demonstration of the applicability of CHS in a clinical setting and its sensitivity to the highly important cerebral microcirculation may open up new opportunities for NIRS applications in research and in medical diagnostics and monitoring.

Practical steps for applying a new dynamic model to near-infrared spectroscopy measurements of hemodynamic oscillations and transient changes: implications for cerebrovascular and functional brain studies.

RATIONALE AND OBJECTIVES: Perturbations in cerebral blood volume (CBV), blood flow (CBF), and metabolic rate of oxygen (CMRO2) lead to associated changes in tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD), which can be measured by near-infrared spectroscopy (NIRS). A novel hemodynamic model has been introduced to relate physiological perturbations and measured quantities. We seek to use this model to determine functional traces of cbv(t) and cbf(t) - cmro2(t) from time-varying NIRS data, and cerebrovascular physiological parameters from oscillatory NIRS data (lowercase letters denote the relative changes in CBV, CBF, and CMRO2 with respect to baseline). Such a practical implementation of a quantitative hemodynamic model is an important step toward the clinical translation of NIRS. MATERIALS AND METHODS: In the time domain, we have simulated O(t) and D(t) traces induced by cerebral activation. In the frequency domain, we have performed a new analysis of frequency-resolved measurements of cerebral hemodynamic oscillations during a paced breathing paradigm. RESULTS: We have demonstrated that cbv(t) and cbf(t) - cmro2(t) can be reliably obtained from O(t) and D(t) using the model, and that the functional NIRS signals are delayed with respect to cbf(t) - cmro2(t) as a result of the blood transit time in the microvasculature. In the frequency domain, we have identified physiological parameters (e.g., blood transit time, cutoff frequency of autoregulation) that can be measured by frequency-resolved measurements of hemodynamic oscillations. CONCLUSIONS: The ability to perform noninvasive measurements of cerebrovascular parameters has far-reaching clinical implications. Functional brain studies rely on measurements of CBV, CBF, and CMRO2, whereas the diagnosis and assessment of neurovascular disorders, traumatic brain injury, and stroke would benefit from measurements of local cerebral hemodynamics and autoregulation.

Validation of a novel hemodynamic model for coherent hemodynamics spectroscopy (CHS) and functional brain studies with fNIRS and fMRI.

We report an experimental validation and applications of the new hemodynamic model presented in the companion article (Fantini, 2014-this issue) both in the frequency domain and in the time domain. In the frequency domain, we have performed diffuse optical measurements for coherent hemodynamics spectroscopy (CHS) on the brain and calf muscle of human subjects, showing that the hemodynamic model predictions (both in terms of spectral shapes and absolute spectral values) are confirmed experimentally. We show how the quantitative analysis based on the new model allows for autoregulation measurements from brain data, and provides an analytical description of near-infrared spiroximetry from muscle data. In the time domain, we have used data from the literature to perform a comparison between brain activation signals measured with functional near-infrared spectroscopy (fNIRS) or with blood oxygenation level dependent (BOLD) fMRI, and the corresponding signals predicted by the new model. This comparison shows an excellent agreement between the model predictions and the reported fNIRS and BOLD fMRI signals. This new hemodynamic model provides a valuable tool for brain studies with hemodynamic-based techniques.

Phase-amplitude investigation of spontaneous low-frequency oscillations of cerebral hemodynamics with near-infrared spectroscopy: a sleep study in human subjects.

We have investigated the amplitude and phase of spontaneous low-frequency oscillations (LFOs) of the cerebral deoxy- and oxy-hemoglobin concentrations ([Hb] and [HbO]) in a human sleep study using near-infrared spectroscopy (NIRS). Amplitude and phase analysis was based on the analytic signal method, and phasor algebra was used to decompose measured [Hb] and [HbO] oscillations into cerebral blood volume (CBV) and flow velocity (CBFV) oscillations. We have found a greater phase lead of [Hb] vs. [HbO] LFOs during non-REM sleep with respect to the awake and REM sleep states (maximum increase in [Hb] phase lead: ~π/2). Furthermore, during non-REM sleep, the amplitudes of [Hb] and [HbO] LFOs are suppressed with respect to the awake and REM sleep states (maximum amplitude decrease: 87%). The associated cerebral blood volume and flow velocity oscillations are found to maintain their relative phase difference during sleep, whereas their amplitudes are attenuated during non-REM sleep. These results show the potential of phase-amplitude analysis of [Hb] and [HbO] oscillations measured by NIRS in the investigation of hemodynamics associated with cerebral physiology, activation, and pathological conditions.