Quantification of cerebral blood flow in adults by contrast-enhanced near-infrared spectroscopy: Validation against MRI.

The purpose of this study was to assess the accuracy of absolute cerebral blood flow (CBF) measurements obtained by dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) using indocyanine green as a perfusion contrast agent. For validation, CBF was measured independently using the MRI perfusion method arterial spin labeling (ASL). Data were acquired at two sites and under two flow conditions (normocapnia and hypercapnia). Depth sensitivity was enhanced using time-resolved detection, which was demonstrated in a separate set of experiments using a tourniquet to temporally impede scalp blood flow. A strong correlation between CBF measurements from ASL and DCE-NIRS was observed (slope = 0.99 ± 0.08, y-intercept = -1.7 ± 7.4 mL/100 g/min, and R2 = 0.88). Mean difference between the two techniques was 1.9 mL/100 g/min (95% confidence interval ranged from -15 to 19 mL/100g/min and the mean ASL CBF was 75.4 mL/100 g/min). Error analysis showed that structural information and baseline absorption coefficient were needed for optimal CBF reconstruction with DCE-NIRS. This study demonstrated that DCE-NIRS is sensitive to blood flow in the adult brain and can provide accurate CBF measurements with the appropriate modeling techniques.

Continuous non-invasive optical monitoring of cerebral blood flow and oxidative metabolism after acute brain injury.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Noninvasive continuous optical monitoring of absolute cerebral blood flow in critically ill adults.

We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient ( γ ) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury ( N = 7 ) is carried out to ascertain the stability of γ . The patient-averaged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24 × 10 9 ( mL / 100 g / min ) / ( cm 2 / s ) was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects.

The critical closing pressure ( CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure ( ABP) at which cerebral blood flow approaches zero, and their difference ( ABP - CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.

Hierarchical clustering method to improve transrectal ultrasound-guided diffuse optical tomography for prostate cancer imaging.

The inclusion of anatomical prior information in reconstruction algorithms can improve the quality of reconstructed images in near-infrared diffuse optical tomography (DOT). Prior literature on possible locations of human prostate cancer from transrectal ultrasound (TRUS), however, is limited and has led to biased reconstructed DOT images. In this work, we propose a hierarchical clustering method (HCM) to improve the accuracy of image reconstruction with limited prior information. HCM reconstructs DOT images in three steps: 1) to reconstruct the human prostate, 2) to divide the prostate region into geometric clusters to search for anomalies in finer clusters, 3) to continue the geometric clustering within anomalies for improved reconstruction. We demonstrated this hierarchical clustering method using computer simulations and laboratory phantom experiments. Computer simulations were performed using combined TRUS/DOT probe geometry with a multilayered model; experimental demonstration was performed with a single-layer tissue simulating phantom. In computer simulations, two hidden absorbers without prior location information were reconstructed with a recovery rate of 100% in their locations and 95% in their optical properties. In experiments, a hidden absorber without prior location information was reconstructed with a recovery rate of 100% in its location and 83% in its optical property.

Sparsity enhanced spatial resolution and depth localization in diffuse optical tomography.

In diffuse optical tomography (DOT), researchers often face challenges to accurately recover the depth and size of the reconstructed objects. Recent development of the Depth Compensation Algorithm (DCA) solves the depth localization problem, but the reconstructed images commonly exhibit over-smoothed boundaries, leading to fuzzy images with low spatial resolution. While conventional DOT solves a linear inverse model by minimizing least squares errors using L2 norm regularization, L1 regularization promotes sparse solutions. The latter may be used to reduce the over-smoothing effect on reconstructed images. In this study, we combined DCA with L1 regularization, and also with L2 regularization, to examine which combined approach provided us with an improved spatial resolution and depth localization for DOT. Laboratory tissue phantoms were utilized for the measurement with a fiber-based and a camera-based DOT imaging system. The results from both systems showed that L1 regularization clearly outperformed L2 regularization in both spatial resolution and depth localization of DOT. An example of functional brain imaging taken from human in vivo measurements was further obtained to support the conclusion of the study.

Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer.

The aim of this study was to develop and characterize multifunctional biodegradable and biocompatible poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with indocyanine green (ICG) as an optical-imaging contrast agent for cancer imaging and as a photothermal therapy agent for cancer treatment. PLGA-ICG nanoparticles (PIN) were synthesized with a particle diameter of 246±11 nm, a polydispersity index of 0.10±0.03, and ICG loading efficiency of 48.75±5.48%. PIN were optically characterized with peak excitation and emission at 765 and 810±5 nm, a fluorescence lifetime of 0.30±0.01 ns, and peak absorbance at 780 nm. The cytocompatibility study of PIN showed 85% cell viability till 1-mg/ml concentration of PIN. Successful cellular uptake of ligand conjugated PIN by prostate cancer cells (PC3) was also obtained. Both phantom-based and in vitro cell culture results demonstrated that PIN (1) have the great potential to induce local hyperthermia (i.e., temperature increase of 8 to 10°C) in tissue within 5 mm both in radius and in depth; (2) result in improved optical stability, excellent biocompatibility with healthy cells, and a great targeting capability; (3) have the ability to serve as an image contrast agent for deep-tissue imaging in diffuse optical tomography.