Journal of Biomedical Optics

In vivo 3D imaging of ovarian cancer outgrowth in transgenic mouse model with optical coherence tomography

Peritoneal dissemination is the major mechanism of how ovarian cancer (OC) spreads. It features tumor outgrowths in the form of multicellular spheroids, their detachment from the primary site, and their implantation in the peritoneal cavity. To understand this process, analyzing the outgrowths at their native locations within the female reproductive system is essential. However, We address this technical challenge by establishing This We present the first This

Iterative prototyping based on lessons learned from the falloposcope in vivo pilot study experience

High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting. The The falloposcope successfully obtained images The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.

Mini review of photoacoustic clinical imaging: a noninvasive tool for disease diagnosis and treatment evaluation

Integrated spectral and depth compensation approach for optimizing oxygen saturation and total hemoglobin estimation in photoacoustic tomography for ovarian lesion diagnosis

Photoacoustic tomography (PAT) holds promise for non-invasive functional imaging in ovarian cancer diagnostics. However, accurate estimation of oxygen saturation ( We aim to improve the accuracy and clinical utility of We introduce a spectral compensation strategy derived from Monte Carlo simulations and integrate it with depth-wise fluence correction to construct the proposed ISDC method. The approach has been validated using phantoms with known optical properties and applied to clinical PAT data from 82 ovarian lesions (67 benign and 15 malignant). Diagnostic performance was evaluated using logistic regression and receiver operating characteristic analysis. In phantom experiments, ISDC improved The ISDC approach significantly enhances the quantitative accuracy and diagnostic performance of PAT by compensating for both spectral and depth fluence variations within biological tissue. These improvements support the integration of ISDC into US-PAT systems for ovarian lesion characterization and future clinical applications.

Circularly polarized light scattering imaging of a cancerous layer creeping under a healthy layer for the diagnosis of early-stage cervical cancer

Cervical cancer progresses through cervical intraepithelial neoplasia (CIN), which are precursor lesions of cervical cancer. In low-grade CIN, atypical cells are generated inside the squamous epithelium, which causes the accuracy of cytodiagnosis for cervical cancer not to be very high. The grade of CIN can be estimated by the depth of atypical cell infiltration from the basal layer to the surface, rather than the abnormality of cells. Therefore, a noninvasive method is required to evaluate the depths of abnormal cells hidden at depth. Cancerous tissues beneath healthy tissues were experimentally identified using circularly polarized light scattering (CiPLS). This method enabled the changes in the size of the cell nuclei within the penetration depth in tissue to be investigated. Artificial unexposed cancerous tissues were prepared that consisted of healthy/cancerous/healthy layers with various thicknesses of the topmost healthy layer and the cancerous layer. A polarization imaging camera with a quarter-wave plate was used to create distribution images of the circular polarization of the scattered light. CiPLS images indicated that the thickness variation of the top healthy layer (the depth of the cancerous layer) caused significant changes in the degree of circular polarization. The depth of unexposed cancer lying within the optical penetration depth can be evaluated using a circular polarization imaging system based on the CiPLS method. These findings will lead to the development of a noninvasive optical diagnostic method for early-stage cervical cancer, potentially improving early detection and treatment outcomes.

Development and clinical validation of a clinically translatable non-chip-on-tip transvaginal imaging system (GynoSight v2.0) for early detection of premalignant cervical lesions

Cervical cancer is the fourth most common cancer among women globally. Hence, it is crucial to develop a noninvasive and portable optical imaging modality for the early detection of premalignant cervical lesions. We present the development and clinical validation of GynoSight v2.0, an indigenously developed multispectral, non-chip-on-tip source, hand-held, portable transvaginal imaging probe, for evaluating tissue health and identifying anomalies, such as those linked to precancerous cervical lesions. GynoSight v2.0 houses a 16 LEDs, 5-megapixel camera, and a Raspberry Pi 5 module. A comparative shadowing effect analysis was performed between GynoSight v2.0 and colposcopy by evaluating statistical metrics such as mean pixel intensity (MPI), shadow area percentage (SAP), entropy, and contrast-to-noise ratio. In addition, the relative oxygen saturation maps of the cervical tissue were computed from the multispectral registered image using the proposed discrete Fourier transform-based image registration technique. The images of The colposcopy images showed more shadowing effects than the GynoSight v2.0 images and hence provide better illumination to aid in better diagnosis.

Polarimetric imaging for cervical pre-cancer screening aided by machine learning: ex vivo studies

Wide-field imaging Mueller polarimetry is an optical imaging technique that has great potential to become a reliable, fast, non-contact We aim to automate/assist with diagnostic segmentation of polarimetric images of uterine cervix specimens. A comprehensive capture-to-classification pipeline is developed in house. Specimens are acquired and measured with imaging Mueller polarimeter and undergo histopathological classification. Subsequently, a labeled dataset is created within tagged regions of either healthy or neoplastic cervical tissues. Several machine learning methods are trained utilizing different training-test-set-split strategies, and their corresponding accuracies are compared. Our results include robust measurements of model performance with two approaches: a 90:10 training-test-set-split and leave-one-out cross-validation. By comparing the classifier's accuracy directly with the ground truth obtained during histology analysis, we demonstrate how conventionally used shuffled split leads to an over-estimate of true classifier performance Combination of Mueller polarimetry and machine learning is a powerful tool for the task of screening for pre-cancerous conditions in cervical tissue sections. Nevertheless, there is a inherent bias with conventional processes that can be addressed using more conservative classifier training approaches. This results in overall improvements of the sensitivity and specificity of the developed techniques for "unseen" images.

Design and implementation of a portable colposcope Mueller matrix polarimeter

Mueller matrix polarimetry can provide useful information about the function and structure of the extracellular matrix. A portable and low-cost system could facilitate the clinical assessment of cervical anomalies in low-resource settings. We introduce a low-cost snapshot Mueller matrix polarimeter that does not require external power, has no moving parts, and can acquire a full Mueller matrix in ∼1  s, to conduct a feasibility study for cervical imaging in the low-resource setting. A snapshot system based on two sets of Savart plates, a ring illuminator with polarizing elements (generating four polarization states), and one camera is introduced. Stokes vectors are formulated to recover the polarization properties of the sample. Then, using Mueller matrix decomposition, the depolarization and retardance information is extracted. We report the results on 16 healthy individuals (out of 22 patients imaged), whose Pap smear showed no malignant findings from mobile clinics in rural region of Mysore, India. The depolarization and retardance information was in agreement with previous reports. We introduce an imaging system and conducted a feasibility study on healthy individuals. This work could futurely translate into diagnostic applications to provide a quantitative platform in the clinical environment (e.g., cervical cancer screening).

Optical imaging for early detection of cervical cancer: state of the art and perspectives

Cervical cancer is one of the major causes of death in females worldwide. HPV infection is the key cause of uncontrolled cell growth leading to cervical cancer. About 90% of cervical cancer is preventable because of the slow progression of the disease, giving a window of about 10 years for the precancerous lesion to be recognized and treated. The present challenges for cervical cancer diagnosis are interobserver variation in clinicians' interpretation of visual inspection with acetic acid/visual inspection with Lugol's iodine, cost of cytology-based screening, and lack of skilled clinicians. The optical modalities can assist in qualitatively and quantitatively analyzing the tissue to differentiate between cancerous and surrounding normal tissues. This work is on the recent advances in optical techniques for cervical cancer diagnosis, which promise to overcome the above-listed challenges faced by present screening techniques. The optical modalities provide substantial measurable information in addition to the conventional colposcopy and Pap smear test to clinically aid the diagnosis. Recent optical modalities on fluorescence, multispectral imaging, polarization-sensitive imaging, microendoscopy, Raman spectroscopy, especially with the portable design and assisted by artificial intelligence, have a significant scope in the diagnosis of premalignant cervical cancer in future.

Sub-millimeter endoscope demonstrates feasibility of in vivo reflectance imaging, fluorescence imaging, and cell collection in the fallopian tubes

Most cases of high-grade serous ovarian carcinoma originate as serous tubal intraepithelial carcinoma (STIC) lesions in the fallopian tube epithelium (FTE), enabling early endoscopic detection. The cell-acquiring fallopian endoscope (CAFE) was built to meet requirements for locating potentially pathological tissue indicated by an alteration in autofluorescence or presence of a targeted fluorophore. A channel was included for directed scrape biopsy of cells from regions of interest. Imaging resolution and fluorescence sensitivity were measured using a standard resolution target and fluorescence standards, respectively. A prototype was tested in ex vivo tissue, and collected cells were counted and processed. Measured imaging resolution was 88  μm at a 5-mm distance, and full field of view was ∼45  deg in air. Reflectance and fluorescence images in ex vivo porcine reproductive tracts were captured, and fit through human tracts was verified. Hemocytometry counts showed that on the order of 105  cells per scrape biopsy could be collected from ex vivo porcine tissue. All requirements for viewing STIC in the FTE were met, and collected cell counts exceeded input requirements for relevant analyses. Our benchtop findings suggest the potential utility of the CAFE device for in vivo imaging and cell collection in future clinical trials.

Beyond light scattering: the effects of intralipid on benzoporphyrin derivative-sensitized photodynamic treatment in ovarian cancer cells

Intralipid, a soybean oil-based lipid emulsion, is widely used in photomedicine to enhance light distribution due to its strong scattering properties. Although the optical characteristics of Intralipid are well documented, interactions with the reactive molecular species (RMS) generated during photodynamic therapy (PDT) and the impact of such interactions on therapeutic outcomes remain poorly understood. We reveal that Intralipid actively influences PDT response We examined how Intralipid affects the optical and photodynamic behavior of benzoporphyrin derivative (BPD), a clinical photosensitizer, in solution and across four ovarian cancer cell lines. The photodynamic properties of BPD, with and without Intralipid, were analyzed using fluorescence spectrometry and RMS probes, and PDT-induced oxidation of Intralipid components was characterized using LC-MS. The effects of Intralipid on BPD-PDT were evaluated under various conditions. Intralipid reduced BPD photobleaching and RMS generation, suggesting RMS quenching. Extensive oxidation of Intralipid components was observed following PDT. Finally, Intralipid significantly modified BPD-PDT efficacy across all four cell lines, depending on photosensitizer-light interval, dose, and incubation time. Intralipid acts as a bioactive modulator of PDT response, highlighting the need for further investigations both