Photoacoustic tomography as a method to estimate the optical fluence distribution in turbid media.

Currently, there are no non-invasive experimental methods available for measuring optical fluence distributions in tissue. We present photoacoustic tomography (PAT) as a method to approximate the relative optical fluence distribution in a homogeneous optically scattering medium. Three-dimensional photoacoustic images were captured with a near-full view PAT scanner in phantoms with known optical absorption and scatter properties. Resultant 3D PAT images were compared to the expected optical fluence distributions from Monte Carlo simulations and diffusion theory using volumetric and shape analysis. Volumetric analysis of PAT images compared well with the optical fluence distributions from simulation. Dice similarity coefficients ranged from 51 to 82%. The reduced scattering coefficient estimated from PAT images compared well to estimates from simulations for values below 0.5 mm-1. Near full-view PAT has been found to be useful for estimating the optical fluence distribution in an optically scattering medium. Further development is needed to extend the measurement range.

Approaching closed spherical, full-view detection for photoacoustic tomography.

SIGNIFICANCE: Photoacoustic tomography (PAT) is a widely explored imaging modality and has excellent potential for clinical applications. On the acoustic detection side, limited-view angle and limited-bandwidth are common key issues in PAT systems that result in unwanted artifacts. While analytical and simulation studies of limited-view artifacts are fairly extensive, experimental setups capable of comparing limited-view to an ideal full-view case are lacking. AIMS: A custom ring-shaped detector array was assembled and mounted to a 6-axis robot, then rotated and translated to achieve up to 3.8π steradian view angle coverage of an imaged object. APPROACH: Minimization of negativity artifacts and phantom imaging were used to optimize the system, followed by demonstrative imaging of a star contrast phantom, a synthetic breast tumor specimen phantom, and a vascular phantom. RESULTS: Optimization of the angular/rotation scans found ≈212 effective detectors were needed for high-quality images, while 15-mm steps were used to increase the field of view as required depending on the size of the imaged object. Example phantoms were clearly imaged with all discerning features visible and minimal artifacts. CONCLUSIONS: A near full-view closed spherical system has been developed, paving the way for future work demonstrating experimentally the significant advantages of using a full-view PAT setup.

The IPASC data format: A consensus data format for photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging modality that has shown promise for improving patient management in a range of applications. Unfortunately, the current lack of uniformity in PAI data formats compromises inter-user data exchange and comparison, which impedes: technological progress; effective research collaboration; and efforts to deliver multi-centre clinical trials. To overcome this challenge, the International Photoacoustic Standardisation Consortium (IPASC) has established a data format with a defined consensus metadata structure and developed an open-source software application programming interface (API) to enable conversion from proprietary file formats into the IPASC format. The format is based on Hierarchical Data Format 5 (HDF5) and designed to store photoacoustic raw time series data. Internal quality control mechanisms are included to ensure completeness and consistency of the converted data. By unifying the variety of proprietary data and metadata definitions into a consensus format, IPASC hopes to facilitate the exchange and comparison of PAI data.

Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3 days after birth.

A major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

Optical monitoring of cerebral perfusion and metabolism in adults during cardiac surgery with cardiopulmonary bypass.

During cardiac surgery with cardiopulmonary bypass (CPB), adequate maintenance of cerebral blood flow (CBF) is vital in preventing postoperative neurological injury - i.e. stroke, delirium, cognitive impairment. Reductions in CBF large enough to impact cerebral energy metabolism can lead to tissue damage and subsequent brain injury. Current methods for neuromonitoring during surgery are limited. This study presents the clinical translation of a hybrid optical neuromonitor for continuous intraoperative monitoring of cerebral perfusion and metabolism in ten patients undergoing non-emergent cardiac surgery with non-pulsatile CPB. The optical system combines broadband near-infrared spectroscopy (B-NIRS) to measure changes in the oxidation state of cytochrome c oxidase (oxCCO) - a direct marker of cellular energy metabolism - and diffuse correlation spectroscopy (DCS) to provide an index of cerebral blood flow (CBFi). As the heart was arrested and the CPB-pump started, increases in CBFi (88.5 ± 125.7%) and significant decreases in oxCCO (-0.5 ± 0.2 µM) were observed; no changes were noted during transitions off CPB. Fifteen hypoperfusion events, defined as large and sustained reductions in CPB-pump flow rate, were identified across all patients and resulted in significant decreases in perfusion and metabolism when mean arterial pressure dropped to 30 mmHg or below. The maximum reduction in cerebral blood flow preceded the corresponding metabolic reduction by 18.2 ± 15.0 s. Optical neuromonitoring provides a safe and non-invasive approach for assessing intraoperative perfusion and metabolism and has potential in guiding patient management to prevent adverse clinical outcomes.

Structured-light surface scanning system to evaluate breast morphology in standing and supine positions.

Breast shapes are affected by gravitational loads and deformities. Measurements obtained in the standing position may not correlate well with measurements in the supine position, which is more representative of patient position during breast surgery. A dual color 3D surface imaging system capable of scanning patients in both supine and standing positions was developed to evaluate the effect of changes in body posture on breast morphology. The system was evaluated with  breast phantoms to assess accuracy, then tested on ten subjects in three body postures to assess its effectiveness as a clinical tool. The accuracy of the system was within 0.4 mm on average across the model. For the human study, there was no effect of body posture on breast volumes (p value > 0.05), but we observed an effect of completeness of breast scans on body posture (p value < 0.05). Post-hoc tests showed that the supine position and the standing position with hands at the waist differed significantly (p value < 0.05). This study shows that the system can quantitatively evaluate the effect of subject postures, and thereby has the potential to be used to investigate peri-operative changes in breast morphology.

Perfusion and Metabolic Neuromonitoring during Ventricular Taps in Infants with Post-Hemorrhagic Ventricular Dilatation.

Post-hemorrhagic ventricular dilatation (PHVD) is characterized by a build-up of cerebral spinal fluid (CSF) in the ventricles, which increases intracranial pressure and compresses brain tissue. Clinical interventions (i.e., ventricular taps, VT) work to mitigate these complications through CSF drainage; however, the timing of these procedures remains imprecise. This study presents Neonatal NeuroMonitor (NNeMo), a portable optical device that combines broadband near-infrared spectroscopy (B-NIRS) and diffuse correlation spectroscopy (DCS) to provide simultaneous assessments of cerebral blood flow (CBF), tissue saturation (StO2), and the oxidation state of cytochrome c oxidase (oxCCO). In this study, NNeMo was used to monitor cerebral hemodynamics and metabolism in PHVD patients selected for a VT. Across multiple VTs in four patients, no significant changes were found in any of the three parameters: CBF increased by 14.6 ± 37.6% (p = 0.09), StO2 by 1.9 ± 4.9% (p = 0.2), and oxCCO by 0.4 ± 0.6 µM (p = 0.09). However, removing outliers resulted in significant, but small, increases in CBF (6.0 ± 7.7%) and oxCCO (0.1 ± 0.1 µM). The results of this study demonstrate NNeMo's ability to provide safe, non-invasive measurements of cerebral perfusion and metabolism for neuromonitoring applications in the neonatal intensive care unit.

Assessing Time-Resolved fNIRS for Brain-Computer Interface Applications of Mental Communication.

Brain-computer interfaces (BCIs) are becoming increasingly popular as a tool to improve the quality of life of patients with disabilities. Recently, time-resolved functional near-infrared spectroscopy (TR-fNIRS) based BCIs are gaining traction because of their enhanced depth sensitivity leading to lower signal contamination from the extracerebral layers. This study presents the first account of TR-fNIRS based BCI for "mental communication" on healthy participants. Twenty-one (21) participants were recruited and were repeatedly asked a series of questions where they were instructed to imagine playing tennis for "yes" and to stay relaxed for "no." The change in the mean time-of-flight of photons was used to calculate the change in concentrations of oxy- and deoxyhemoglobin since it provides a good compromise between depth sensitivity and signal-to-noise ratio. Features were extracted from the average oxyhemoglobin signals to classify them as "yes" or "no" responses. Linear-discriminant analysis (LDA) and support vector machine (SVM) classifiers were used to classify the responses using the leave-one-out cross-validation method. The overall accuracies achieved for all participants were 75% and 76%, using LDA and SVM, respectively. The results also reveal that there is no significant difference in accuracy between questions. In addition, physiological parameters [heart rate (HR) and mean arterial pressure (MAP)] were recorded on seven of the 21 participants during motor imagery (MI) and rest to investigate changes in these parameters between conditions. No significant difference in these parameters was found between conditions. These findings suggest that TR-fNIRS could be suitable as a BCI for patients with brain injuries.

Development of a Human Photoacoustic Imaging Reporter Gene Using the Clinical Dye Indocyanine Green.

Purpose: To develop a photoacoustic imaging (PAI) reporter gene that has high translational potential. Previous research has shown that human organic anion-transporting polypeptide 1b3 (OATP1B3) promotes the uptake of the near-infrared fluorescent dye indocyanine green (ICG). In this study, the authors have established OATP1B3 and ICG as a reporter gene-probe pair for in vivo PAI. Materials and Methods: Human breast cancer cells were engineered to express OATP1B3. Control cells (not expressing OATP1B3) or OATP1B3-expressing cells were incubated with or without ICG, placed in a breast-mimicking phantom, and imaged with PAI. Control (n = 6) or OATP1B3-expressing (n = 5) cells were then implanted orthotopically into female mice. Full-spectrum PAI was performed before and 24 hours after ICG administration. One-way analysis of variance was performed, followed by Tukey posthoc multiple comparisons, to assess statistical significance. Results: OATP1B3-expressing cells incubated with ICG exhibited a 2.7-fold increase in contrast-to-noise ratio relative to all other controls in vitro (P < .05). In mice, PAI signals after ICG administration were increased 2.3-fold in OATP1B3 tumors relative to those in controls (P < .05). Conclusion: OATP1B3 operates as an in vivo PAI reporter gene based on its ability to promote the cellular uptake of ICG. Benefits include the human derivation of OATP1B3, combined with the use of wavelengths in the near-infrared region, high extinction coefficient, low quantum yield, and clinical approval of ICG. The authors posit that this system will be useful for localized monitoring of emerging gene- and cell-based therapies in clinical applications.© RSNA, 2019Keywords: Animal Studies, Molecular Imaging, Molecular Imaging-Clinical Translation, Molecular Imaging-Reporter Gene Imaging, Optical ImagingSupplemental material is available for this article.