Dynamic Optical Coherence Tomography Research Articles

An Optical Tomography-Based Score to Assess Pediatric Hand Burns

To define the morphologic pattern of pediatric hand burns as visualized via optical coherence tomography (OCT) and dynamic OCT (D-OCT). We designed a scoring system to assess the depths of burn wounds on pediatric hands and tested this score in our cohort of children with burn injuries to the hand. Overall, 67 hand burns in 48 children (0–15 years) were prospectively examined. Scans were interpreted by two independent observers. Relevant OCT findings were surface irregularity, loss of epidermis, loss of dermal pattern (skin lines or papillary spots, loss of surface regularity and irregular vascular pattern of the plexus papillaris. Score values were calculated retrospectively. A score of 4 was associated with spontaneous healing without the need for skin grafting, with a positive predictive value of 97%. Deeper wounds with delayed healing and/or the need of skin grafting received a score of 5 or above, with an agreement of medical healing in 80% and a positive predictive value of 56%. OCT and D-OCT provide clinically useful additional information in cases of pediatric hand burns. The OCT burn score has the potential to support clinical decision making and, subsequently, improve clinical outcomes and shorten hospital stays.

Abstract PO5-07-05: Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery

Abstract Background: Reliable identification of axillary lymph node (ALN) involvement in patients with breast cancer allows for definitive axillary dissection at the time of the initial surgery, thus avoiding the need for a separate axillary surgery. However, conventional intraoperative ALN diagnostic methods are time-consuming and labor-intensive and can result in tissue destruction. Dynamic full field optical coherence tomography, also called dynamic cell imaging (DCI), has been developed and validated to offer rapid and label-free histologic approximations of metastatic and non-metastatic ALNs. In this study, we aim to optimize the diagnostic pipeline with an automated approach and present the results of using a deep learning (DL) algorithm with DCI to predict ALN status intraoperatively in patients with breast cancer. Methods: Breast cancer patients who required ALN staging were enrolled prospectively in this study. DCI was applied to bisected fresh lymph nodes in a non-destructive manner, and the specimens were subsequently sent for histopathological examination, regarded as the gold standard for comparison. A DL model was trained and fine-tuned on over 80,000 DCI images, and the results were mapped to slide level to predict ALN diagnosis. Results: Total 607 DCI slides of ALNs with 112,852 cropped patches were included in the study. The DL model was trained and validated on a dataset containing 481 slides and tested on an independent testing dataset with 126 slides. In the test set, the DL algorithm yielded accuracy for prediction of ALN status, with sensitivity and specificity of 91.9% and 95.5% and an area under the receiver operating characteristic curve (AUC) of 0.937 (95% confidence interval [CI]: 0.912-0.957) at slide level. Conclusion: These results demonstrate that the integration of DCI with DL is rapid, reduces labor requirements and minimizes tissue destruction. Meanwhile, this algorithm had high classification accuracy to predict the metastatic burden of ALNs for patients with breast cancer. Citation Format: Shuwei Zhang, Houpu Yang, Jin Zhao, Shu Wang. Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-05.

Tirbanibulin 1% Ointment Effectiveness for Actinic Keratosis Treatment Evaluated by Dynamic Optical Coherence Tomography

Background. Actinic keratosis (AK) is a common premalignant skin condition. Its diagnosis is based on a clinical and sometimes dermoscopic examination, but, in some situations, a skin biopsy may be necessary. Dynamic optical coherence tomography (D-OCT) can often bypass this need, by noninvasive evaluation of skin morphology. Early and effective treatment of AKs is important to prevent the progression to invasive squamous cell carcinoma (iSCC). Tirbanibulin 1% ointment, a new topical field therapy for AKs, has recently been introduced. Objectives. The aim of this study was to evaluate the efficacy and safety of tirbanibulin 1% ointment for the field treatment of nonhyperkeratotic, nonhypertrophic AKs (Olsen grade 1) on the face and/or scalp in adults, using D-OCT technology. Methods. Patients, presenting multiple, mild to moderate AKs on the face and scalp, in treatment with tirbanibulin 1% ointment for five consecutive days of an area measuring 25 cm2, were evaluated with videodermoscopy (V-track Vidix 4.0) and D-OCT (VivoSight Dx, Michelson Diagnostics Ltd., Kent, England, United Kingdom), as normal clinical practice. The lesions were staged according to the Olsen classification, excluding the most aggressive lesions. Results. We retrospectively evaluated 50 patients (27 males and 23 females, mean age 76 ± 7.9 years). At 57 days posttreatment, the complete clearance rate was 68% (n = 34) and partial clearance rate was 76% (n = 38). D-OCT showed markedly improved morphology, including a better recognizable dermal-epidermal junction (DEJ), associated with reduced inflammation. The most common adverse events reported were erythema and scaling, which were mostly mild and self-limiting. Conclusions. This study demonstrated that tirbanibulin may be considered an effective and well-tolerated treatment option for nonhyperkeratotic, nonhypertrophic AKs. It showed a favorable safety profile, with mostly mild adverse events. D-OCT can be considered a useful tool for personalizing AK treatment and monitoring.

Neural-network based high-speed volumetric dynamic optical coherence tomography

Neural-network based high-speed volumetric dynamic optical coherence tomography

A tricky singular papular peri‐cicatricial mammarian lesion

AbstractBreast cancer represents the most common malignancy in women worldwide. In most cases, metastasis is the leading cause of mortality. Early diagnosis is still challenging despite standardised, government‐led screening programs, but is crucial in achieving improved survival rates. Additionally, a deeper understanding of the metastatic potential of breast cancer is critical for developing therapeutic interventions to combat widespread disease. Cutaneous metastasis from underlying breast carcinoma is uncommon as the first manifestation of visceral malignancies and is commonly observed in advanced‐stage malignancies, often associated with poor prognosis, and a prompt, precise tissue diagnosis is mandatory. A high index of suspicion in oncologic patients is required to diagnose these lesions, as they can mimic benign skin manifestations and clinical findings may be subtle and going unnoticed. We report on a case of a 76‐year‐old female patient presenting to our non‐invasive diagnostic outpatient clinic with an unusual cutaneous presentation, as an early sign of locally advanced invasive ductal carcinoma breast cancer recurrence. The aim of our article is to underline the importance of the dermatologist in the multi‐disciplinary oncologic diagnostic process, including non‐invasive imaging evaluation of cutaneous lesions, especially insidious breast carcinomas. Dynamic optical coherence tomography (D‐OCT) is not routinely used due to its cost, therefore lesion's aspect has not been completely described, consequently, the correct evaluation of skin architecture appearance can add important information, especially in cutaneous oncology where it can help in early diagnosis or cancer recurrency. OCT may contribute to the detection of subclinical cutaneous manifestations of cancer or recurrence, in particular, when they are difficult to differentiate clinically from benign lesion. In the case we described, OCT of suspected lesion showed the loss of the DEJ with solid nests and irregular vessels.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Label-free visualization and quantification of the drug-type-dependent response of tumor spheroids by dynamic optical coherence tomography

We demonstrate label-free dynamic optical coherence tomography (D-OCT)-based visualization and quantitative assessment of patterns of tumor spheroid response to three anti-cancer drugs. The study involved treating human breast adenocarcinoma (MCF-7 cell-line) with paclitaxel (PTX), tamoxifen citrate (TAM), and doxorubicin (DOX) at concentrations of 0 (control), 0.1, 1, and 10 µM for 1, 3, and 6 days. In addition, fluorescence microscopy imaging was performed for reference. The D-OCT imaging was performed using a custom-built OCT device. Two algorithms, namely logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDSl\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_l$$\\end{document}) were used to visualize the tissue dynamics. The spheroids treated with 0.1 and 1 µM TAM appeared similar to the control spheroid, whereas those treated with 10 µM TAM had significant structural corruption and decreasing LIV and OCDSl\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_l$$\\end{document} over treatment time. The spheroids treated with PTX had decreasing volumes and decrease of LIV and OCDSl\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_l$$\\end{document} signals over time at most PTX concentrations. The spheroids treated with DOX had decreasing and increasing volumes over time at DOX concentrations of 1 and 10 µM, respectively. Meanwhile, the LIV and OCDSl\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_l$$\\end{document} signals decreased over treatment time at all DOX concentrations. The D-OCT, particularly OCDSl\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_l$$\\end{document}, patterns were consistent with the fluorescence microscopic patterns. The diversity in the structural and D-OCT results among the drug types and among the concentrations are explained by the mechanisms of the drugs. The presented results suggest that D-OCT is useful for evaluating the difference in the tumor spheroid response to different drugs and it can be a useful tool for anti-cancer drug testing.

Comparative oncology chemosensitivity assay for personalized medicine using low-coherence digital holography of dynamic light scattering from cancer biopsies

Nearly half of cancer patients who receive standard-of-care treatments fail to respond to their first-line chemotherapy, demonstrating the pressing need for improved methods to select personalized cancer therapies. Low-coherence digital holography has the potential to fill this need by performing dynamic contrast OCT on living cancer biopsies treated ex vivo with anti-cancer therapeutics. Fluctuation spectroscopy of dynamic light scattering under conditions of holographic phase stability captures ultra-low Doppler frequency shifts down to 10 mHz caused by light scattering from intracellular motions. In the comparative preclinical/clinical trials presented here, a two-species (human and canine) and two-cancer (esophageal carcinoma and B-cell lymphoma) analysis of spectral phenotypes identifies a set of drug response characteristics that span species and cancer type. Spatial heterogeneity across a centimeter-scale patient biopsy sample is assessed by measuring multiple millimeter-scale sub-samples. Improved predictive performance is achieved for chemoresistance profiling by identifying red-shifted sub-samples that may indicate impaired metabolism and removing them from the prediction analysis. These results show potential for using biodynamic imaging for personalized selection of cancer therapy.

Diagnostic Imaging of Agminated Blue Lesions and Blue Lesions with Satellitosis: Case Series with a Concise Review of the Current Literature

Background: Agmination and/or satellitosis in pigmented blue lesions is a phenomenon rarely mentioned in the literature and not well known. This phenomenon can be expressed by several benign and malignant pigmented blue lesions, such as blue nevi, Spitz nevi, melanocytoma and melanoma. On this spectrum, dermoscopy, reflectance confocal microscopy (RCM) and dynamic Optical coherence tomography (D-OCT) represent non-invasive imaging technologies, which may help clinicians in the diagnosis of melanoma and non-melanoma skin cancers in daily clinical practice. Methods: Currently, in the literature there is a lack of new data about agminated blue lesions and blues lesions with satellitosis, as well as the lack of a recent and updated review of the literature about this topic. Therefore, considering that clinicians must be confident with the diagnosis of these rare skin lesions, we decided to carry out this work. Results: In this paper, four new cases of agminated pigmented cutaneous lesions were described. Moreover, a review of the current literature on this topic was performed. Conclusions: A clinical–pathological correlation is often needed to reach a correct diagnosis; currently, dermoscopy and non-invasive diagnostic techniques, such as reflectance confocal microscopy and optical coherence tomography, due to the depth of these skin lesions in the dermis, can only make a partial and limited contribution.

Intrinsic signal optoretinography of dark adaptation abnormality due to rod photoreceptor degeneration.

This research aims to investigate the potential of using intrinsic optical signal (IOS) optoretinography (ORG) to objectively detect dark adaptation (DA) abnormalities related to rod photoreceptor degeneration. Functional optical coherence tomography (OCT) was employed in both wild-type (WT) and retinal degeneration 10 (rd10) mice to conduct this assessment. Dynamic OCT measurements captured the changes in retinal thickness and reflectance from light-to-dark transition. Comparative analysis revealed significant IOS alterations within the outer retina. Specifically, a reduction in thickness from external limiting membrane (ELM) peak to retinal pigment epithelium (RPE) peak was observed (WT: 1.13 ± 0.69µm, 30min DA; rd10: 2.64 ± 0.86µm, 30min DA), as well as a decrease in the intensity of the inner segment ellipsoid zone (EZ) in 30min DA compared to light adaptation (LA). The reduction of relative EZ intensity was notable in rd10 after 5min DA and in WT after 15min DA, with a distinguishable difference between rd10 and WT after 10min DA. Furthermore, our findings indicated a significant decrease in the relative intensity of the hypo-reflective band between EZ and RPE in rd10 retinas during DA, which primarily corresponds to the outer segment (OS) region. In conclusion, the observed DA-IOS abnormalities, including changes in ELM-RPE thickness, EZ, and OS intensity, hold promise as differentiators between WT and rd10 mice before noticeable morphological abnormalities occur. These findings suggest the potential of this non-invasive imaging technique for the early detection of dysfunction in retinal photoreceptors.

Evaluating the performance of OCT in assessing static and potential dynamic properties of the retinal ganglion cells and nerve fiber bundles in the living mouse eye.

Glaucoma is a group of eye diseases characterized by the thinning of the retinal nerve fiber layer (RNFL), which is primarily caused by the progressive death of retinal ganglion cells (RGCs). Precise monitoring of these changes at a cellular resolution in living eyes is significant for glaucoma research. In this study, we aimed to assess the effectiveness of temporal speckle averaging optical coherence tomography (TSA-OCT) and dynamic OCT (dOCT) in examining the static and potential dynamic properties of RGCs and RNFL in living mouse eyes. We evaluated parameters such as RNFL thickness and possible dynamics, as well as compared the ganglion cell layer (GCL) soma density obtained from in vivo OCT, fluorescence scanning laser ophthalmoscopy (SLO), and ex vivo histology.

Immediate diagnosis of cutaneous metastases with optical coherence tomography, line‐field confocal optical coherence tomography and dermoscopy: A case series

AbstractBackgroundCutaneous metastases (CM) are a frequent finding in the follow‐up of malignant tumours.ObjectivesCM were examined with dermoscopy, optical coherence tomography (OCT), dynamic OCT and line‐field confocal OCT (LC‐OCT) to describe common findings.MethodsIn the University Hospital Carl Gustav Carus Dresden, Germany, 18 patients with 61 CM were examined with dermoscopy. CM (n = 43, 31 melanoma metastases, two metastases of renal carcinoma, five metastases of cutaneous squamous cell carcinoma and five metastases of pleomorphic dermal sarcoma) were examined with OCT (VivoSight® Michelson Diagnostics). Additional 18 melanoma metastases were examined with LC‐OCT (deepLive™; Damae Medical).ResultsCM were localized on the head, trunk, neck and limbs. Dermoscopy patterns were angioma‐like, nevus‐like nonglobular, nevus‐like globular, blue nevus‐like and unspecific. CM showed an ulceration, hyperkeratosis with increased entrance signal and disturbed architecture of the epidermis in OCT. In deeper metastases, the dermoepidermal junction (DEJ) was normal; in most cases it was disturbed. CM were visible as subepidermal hyporeflective roundish area, with septae, with either clear margin and shadowing or blurred margin. DOCT showed dot, coiled, serpiginous and branched vessels; there was a disarray in size and distribution and vessels were converging on the centre of the metastasis. In LC‐OCT, CM showed enhanced entrance signal and disturbed architecture of a thinned epidermis, ulceration, atypical honeycomb or cobblestone pattern as well as a broken DEJ. In the dermis, a hyporeflective roundish area with clusters of hyporeflective cells with septae, clear margin and clefting or blurred margin was visible; the hyporeflective area was surrounded by bundles of connective tissue. Subepidermal vessels differentiated in size and distribution. Inflammatory, dendritic and pagetoid cells were visible.ConclusionsOCT and LC‐OCT may be useful tools for immediate diagnosis, localization of CM and monitoring under treatment in addition to conventional methods like ultrasound and histopathology.

In vivo volumetric depth-resolved imaging of cilia metachronal waves using dynamic optical coherence tomography.

Motile cilia are dynamic hair-like structures covering epithelial surfaces in multiple organs. The periodic coordinated beating of cilia creates waves propagating along the surface, known as the metachronal waves, which transport fluids and mucus along the epithelium. Motile ciliopathies result from disrupted coordinated cilia beating and are associated with serious clinical complications, including reproductive disorders. Despite the recognized clinical significance, research of cilia dynamics is extremely limited. Here, we present quantitative imaging of cilia metachronal waves volumetrically through tissue layers using dynamic optical coherence tomography (OCT). Our method relies on spatiotemporal mapping of the phase of intensity fluctuations in OCT images caused by the ciliary beating. We validated our new method ex vivo and implemented it in vivo to visualize cilia metachronal wave propagation within the mouse fallopian tube. This method can be extended to the assessment of physiological cilia function and ciliary dyskinesias in various organ systems, contributing to better management of pathologies associated with motile ciliopathies.

Value of high-resolution full-field optical coherence tomography and dynamic cell imaging for one-stop rapid diagnosis breast clinic.

Full-field optical coherence tomography combined with dynamic cell imaging (D-FFOCT) is a new, simple-to-use, nondestructive, quick technique that can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. Dynamic full-field optical coherence tomography was applied to fresh, untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon, and pathologist) analyzed the samples without knowing final histological diagnosis or American College of Radiology classification. The results were compared to conventional processing and staining (hematoxylin-eosin). A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49.27%), 99 benign lesions (48.29%), 3 ductal in situ carcinoma (1.46%), and 2 atypias (0.98%). The diagnostic performance results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78], and NPV: 75% [0.72;0.78]. A large image atlas was created as well as a diagnosis algorithm from the readers' experience. With 74% PPV and 75% NPV, D-FFOCT is not yet ready to be used in clinical practice to identify breast cancer. This is mainly explained by the lack of experience and knowledge of this new technic by the four lectors. By training with the diagnosis algorithm and the image atlas, radiologists could have better outcomes allowing quick detection of breast cancer and lymph node involvement. Deep learning could also be used, and further investigation will follow.

Dynamic full-field optical coherence tomography module adapted to commercial microscopes allows longitudinal in vitro cell culture study

Dynamic full-field optical coherence tomography (D-FFOCT) has recently emerged as a label-free imaging tool, capable of resolving cell types and organelles within 3D live samples, whilst monitoring their activity at tens of milliseconds resolution. Here, a D-FFOCT module design is presented which can be coupled to a commercial microscope with a stage top incubator, allowing non-invasive label-free longitudinal imaging over periods of minutes to weeks on the same sample. Long term volumetric imaging on human induced pluripotent stem cell-derived retinal organoids is demonstrated, highlighting tissue and cell organization processes such as rosette formation and mitosis as well as cell shape and motility. Imaging on retinal explants highlights single 3D cone and rod structures. An optimal workflow for data acquisition, postprocessing and saving is demonstrated, resulting in a time gain factor of 10 compared to prior state of the art. Finally, a method to increase D-FFOCT signal-to-noise ratio is demonstrated, allowing rapid organoid screening.

Dynamic optical coherence tomography of chronic venous ulcers.

Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.

Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography

This study aims at demonstrating label-free drug-response-patterns assessment of different tumor spheroids and drug types by dynamic optical coherence tomography (D-OCT). The study involved human breast cancer (MCF-7) and colon cancer (HT-29) spheroids. The MCF-7 and HT-29 spheroids were treated with paclitaxel (Taxol; PTX) and the active metabolite of irinotecan SN-38, respectively. The drugs were applied with 0 (control), 0.1, 1, and 10 μM concentrations and the treatment durations were 1, 3, and 6 days. A swept-source OCT microscope equipped with a repeated raster scanning protocol was used to scan the spheroids. Logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS_l) algorithms were used to visualize the tumor spheroid dynamics. LIV and OCDS_l images visualized different response patterns of the two types of spheroids. In addition, spheroid morphology, LIV, and OCDS_l quantification showed different time-courses among the spheroid and drug types. These results may indicate different action mechanisms of the drugs. The results showed the feasibility of D-OCT for the evaluation of drug response patterns of different cell spheroids and drug types and suggest that D-OCT can perform anti-cancer drug testing.

Renal tubular function and morphology revealed in kidney without labeling using three-dimensional dynamic optical coherence tomography

Renal tubule has distinct metabolic features and functional activity that may be altered during kidney disease. In this paper, we present label-free functional activity imaging of renal tubule in normal and obstructed mouse kidney models using three-dimensional (3D) dynamic optical coherence tomography (OCT) ex vivo. To create an obstructed kidney model, we ligated the ureter of the left kidney for either 7 or 14 days. Two different dynamic OCT (DOCT) methods were implemented to access the slow and fast activity of the renal tubules: a logarithmic intensity variance (LIV) method and a complex-correlation-based method. Three-dimensional DOCT data were acquired with a 1.3 upmum swept-source OCT system and repeating raster scan protocols. In the normal kidney, the renal tubule appeared as a convoluted pipe-like structure in the DOCT projection image. Such pipe-like structures were not observed in the kidneys subjected to obstruction of the ureter for several days. Instead of any anatomical structures, a superficial high dynamics appearance was observed in the perirenal cortex region of the obstructed kidneys. These findings suggest that volumetric LIV can be used as a tool to investigate kidney function during kidney diseases.

Dynamic Optical Coherence Tomography of Blood Vessels in Cutaneous Melanoma-Correlation with Histology, Immunohistochemistry and Dermoscopy.

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery.

Raynaud phenomenon and microvasculopathy in systemic sclerosis: multi-modality imaging for diagnosis and evaluation.

To describe the clinical significance of and the diagnostic approach to Raynaud phenomenon (RP) in the peripheral extremities and the heart. Nailfold capillaroscopy has recently been standardized in an expert consensus paper. Abnormal capillaroscopy in combination with specific autoantibody profiles and clinical signs are highly predictive of progression of RP to systemic sclerosis (SSc). Magnetic resonance imaging (MRI) can also perform tissue characterization of both the extremities and the heart. Microvascular wall abnormalities detected using nailfold capillaroscopy in patients with SSc may lead to deposition of erythrocyte-derived iron, due to microhemorrhages, which may predispose to fibrosis. MRI can assess the presence of iron using T2∗ measurements. RP is a hallmark of the microvasculopathy in SSc and can affect both the peripheral extremities and the heart. Nailfold capillaroscopy is the current gold standard for the evaluation of the peripheral microvasculature. Other imaging modalities include thermography, laser Doppler-derived methods, 99mTc-pertechnetate hand perfusion scintigraphy, power Doppler ultrasonography, dynamic optical coherence tomography, MRI, and photoacoustic imaging, but these are currently not widely used. Cardiac RP can be investigated with positron emission tomography or cardiovascular magnetic resonance, with the latter offering the additional possibility of tissue characterization and iron content quantification secondary to microhemorrhages.