Journal of Biomedical Optics最新文献

[This corrects the article DOI: 10.1117/1.JBO.28.4.046002.].

Significance: The ability to observe and monitor cell density and morphology has been imperative for assessing the health of a cell culture and for producing high quality, high yield cell cultures for decades. Microcarrier-based cultures, used for large-scale cellular expansion processes, are not compatible with traditional visualization-based methods, such as widefield microscopy, due to their thickness and material composition.

Aim: Here, we assess the optical imaging compatibilities of commercial polystyrene microcarriers versus custom-fabricated gelatin methacryloyl (gelMA) microcarriers for non-destructive and non-invasive visualization of the entire microcarrier surface, direct cell enumeration, and sub-cellular visualization of mesenchymal stem/stromal cells.

Approach: Mie scattering and wavefront error simulations of the polystyrene and gelMA microcarriers were performed to assess the potential for elastic scattering-based imaging of adherent cells. A Zeiss Z.1 light-sheet microscope was adapted to perform light-sheet tomography using label-free elastic scattering contrast from planar side illumination to achieve optical sectioning and permit non-invasive and non-destructive, in toto, three-dimensional, high-resolution visualization of cells cultured on microcarriers.

Results: The polystyrene microcarrier prevents visualization of cells on the distal half of the microcarrier using either fluorescence or elastic scattering contrast, whereas the gelMA microcarrier allows for high fidelity visualization of cell morphology and quantification of cell density using light-sheet fluorescence microscopy and tomography.

Conclusions: The combination of optical-quality gelMA microcarriers and label-free light-sheet tomography will facilitate enhanced control of bioreactor-microcarrier cell culture processes.

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes.

Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT.

Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers.

Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles ($p=0.042$). In addition, the change in normalized tumor ${\mathrm{StO}}_2$ upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle ($p=0.038$). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI.

Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation.

Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest.

Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared.

Results: Diabetic patients showed significantly reduced mean BF in the neurogenic ($p=0.044$) and heart ($p=0.001$) components at the M1 and M5 regions ($p=0.025$) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic ($p=0.049$) and myogenic ($p=0.032$) components at the M1 region, as well as in the endothelial ($p<0.001$) component at the M5 region and in the myogenic component at the dorsal foot ($p=0.007$), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region ($p=0.050$) and heel area ($p=0.041$). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region ($p=0.017$) and heel area ($p=0.028$) in diabetic patients.

Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Significance: Photoacoustic computed tomography (PACT) is a promising non-invasive imaging technique for both life science and clinical implementations. To achieve fast imaging speed, modern PACT systems have equipped arrays that have hundreds to thousands of ultrasound transducer (UST) elements, and the element number continues to increase. However, large number of UST elements with parallel data acquisition could generate a massive data size, making it very challenging to realize fast image reconstruction. Although several research groups have developed GPU-accelerated method for PACT, there lacks an explicit and feasible step-by-step description of GPU-based algorithms for various hardware platforms.

Aim: In this study, we propose a comprehensive framework for developing GPU-accelerated PACT image reconstruction (GPU-accelerated photoacoustic computed tomography), to help the research community to grasp this advanced image reconstruction method.

Approach: We leverage widely accessible open-source parallel computing tools, including Python multiprocessing-based parallelism, Taichi Lang for Python, CUDA, and possible other backends. We demonstrate that our framework promotes significant performance of PACT reconstruction, enabling faster analysis and real-time applications. Besides, we also described how to realize parallel computing on various hardware configurations, including multicore CPU, single GPU, and multiple GPUs platform.

Results: Notably, our framework can achieve an effective rate of $\sim 871$ times when reconstructing extremely large-scale three-dimensional PACT images on a dual-GPU platform compared to a 24-core workstation CPU. In this paper, we share example codes via GitHub.

Conclusions: Our approach allows for easy adoption and adaptation by the research community, fostering implementations of PACT for both life science and medicine.

Significance: The estimation of tissue optical properties using diffuse optics has found a range of applications in disease detection, therapy monitoring, and general health care. Biomarkers derived from the estimated optical absorption and scattering coefficients can reflect the underlying progression of many biological processes in tissues.

Aim: Complex light-tissue interactions make it challenging to disentangle the absorption and scattering coefficients, so dedicated measurement systems are required. We aim to help readers understand the measurement principles and practical considerations needed when choosing between different estimation methods based on diffuse optics.

Approach: The estimation methods can be categorized as: steady state, time domain, time frequency domain (FD), spatial domain, and spatial FD. The experimental measurements are coupled with models of light-tissue interactions, which enable inverse solutions for the absorption and scattering coefficients from the measured tissue reflectance and/or transmittance.

Results: The estimation of tissue optical properties has been applied to characterize a variety of ex vivo and in vivo tissues, as well as tissue-mimicking phantoms. Choosing a specific estimation method for a certain application has to trade-off its advantages and limitations.

Conclusion: Optical absorption and scattering property estimation is an increasingly important and accessible approach for medical diagnosis and health monitoring.

Significance: Pulsatile blood oxygen saturation ( ${\mathrm{SpO}}_2$ ) via pulse oximetry is a valuable clinical metric for assessing oxygen delivery. Individual anatomical features, including skin tone, may affect current optical pulse oximetry methods.

Aim: We developed an optical pulse oximetry method based on dual-ratio (DR) measurements to suppress individual anatomical confounds on ${\mathrm{SpO}}_2$ .

Approach: We designed a DR-based finger pulse oximeter, hypothesizing that DR would suppress confounds from optical coupling and superficial tissue absorption. This method is tested using Monte Carlo simulations and in vivo experiments.

Results: Different melanosome volume fractions in the epidermis, a surrogate for skin tone, cause changes in the recovered ${\mathrm{SpO}}_2$ on the order of 1% in simulation and in vivo. Different heterogeneous pulsatile hemodynamics cause greater changes on the order of 10% in simulations. ${\mathrm{SpO}}_2$ recovered with DR measurements showed less variability than the traditional single-distance (SD) transmission method.

Conclusions: For the models and methods considered here, ${\mathrm{SpO}}_2$ measurements are strongly impacted by heterogeneous pulsatile hemodynamics. This variability may be larger than the skin tone bias, which is a known confound in ${\mathrm{SpO}}_2$ measurements. The partial suppression of variability in the ${\mathrm{SpO}}_2$ recovered by DR suggests the promise of DR for pulse oximetry.

Significance: Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is non-specific, frequently leading to misdiagnosis and delays in care. No current strategies yield an accurate, real-time diagnosis of an NSTI.

Aim: A first-in-kind, observational, clinical pilot study tested the hypothesis that measurable fluorescence signal voids occur in NSTI-affected tissues following intravenous administration and imaging of perfusion-based indocyanine green (ICG) fluorescence. This hypothesis is based on the established knowledge that NSTI is associated with local microvascular thrombosis.

Approach: Adult patients presenting to the Emergency Department of a tertiary care medical center at high risk for NSTI were prospectively enrolled and imaged with a commercial fluorescence imager. Single-frame fluorescence snapshot and first-pass perfusion kinetic parameters-ingress slope (IS), time-to-peak (TTP) intensity, and maximum fluorescence intensity (IMAX)-were quantified using a dynamic contrast-enhanced fluorescence imaging technique. Clinical variables (comorbidities, blood laboratory values), fluorescence parameters, and fluorescence signal-to-background ratios (SBRs) were compared to final infection diagnosis.

Results: Fourteen patients were enrolled and imaged (six NSTI, six cellulitis, one diabetes mellitus-associated gangrene, and one osteomyelitis). Clinical variables demonstrated no statistically significant differences between NSTI and non-NSTI patient groups ($p\text{-value}\ge 0.22$). All NSTI cases exhibited prominent fluorescence signal voids in affected tissues, including tissue features not visible to the naked eye. All cellulitis cases exhibited a hyperemic response with increased fluorescence and no distinct signal voids. Median lesion-to-background tissue SBRs based on snapshot, IS, TTP, and IMAX parameter maps ranged from 3.2 to 9.1, 2.2 to 33.8, 1.0 to 7.5, and 1.5 to 12.7, respectively, for the NSTI patient group. All fluorescence parameters except TTP demonstrated statistically significant differences between NSTI and cellulitis patient groups ($p\text{-value}<0.05$).

Conclusions: Real-time, accurate discrimination of NSTIs compared with non-necrotizing infections may be possible with perfusion-based ICG fluorescence imaging.

Significance: Scanning laser optical tomography (SLOT) is a volumetric multi-modal imaging technique that is comparable to optical projection tomography and computer tomography. Image quality is crucially dependent on matching the refractive indexes (RIs) of the sample and surrounding medium, but RI matching often requires some effort and is never perfect.

Aim: Reducing the burden of RI matching between the immersion medium and sample in biomedical imaging is a challenging and interesting task. We aim at implementing a post processing strategy for correcting SLOT measurements that have errors caused by RI mismatch.

Approach: To better understand the problems with poorly matched Ris, simulated SLOT measurements with imperfect RI matching of the sample and medium are performed and presented here. A method to correct distorted measurements was developed and is presented and evaluated. This method is then applied to a sample containing fluorescent polystyrene beads and a sample made of olydimethylsiloxane with embedded fluorescent nanoparticles.

Results: From the simulations, it is evident that measurements with an RI mismatch larger than 0.02 and no correction yield considerably worse results compared to perfectly matched measurements. RI mismatches larger than 0.05 make it almost impossible to resolve finer details and structures. By contrast, the simulations imply that a measurement with an RI mismatch of up to 0.1 can still yield reasonable results if the presented correction method is applied. The experiments validate the simulated results for an RI mismatch of about 0.09.

Conclusions: The method significantly improves the SLOT image quality for samples with imperfectly matched Ris. Although the absolutely best imaging quality will be achieved with perfect RI matching, these results pave the way for imaging in SLOT with RI mismatches while maintaining high image quality.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS).

Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery.

Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts.

Results: In the first protocol ($28\pm 5$ years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients ($65\pm 15$ years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed.

Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.