BLI Publications

Fibrin glue mediated direct delivery of radiation sensitizers results in enhanced efficacy of radiation treatment.

(2024)

PURPOSE: Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled with the need to consider the tolerance of normal tissues and the potential effects on neurocognitive function, impose constraints on the amount of RT that can be safely delivered. A strategy for augmenting the effectiveness of RT involves the utilization of radiation sensitizers (RS). Directly implanting RS-loaded fibrin glue (FG) into the tumor resection cavity would by-pass the blood brain barrier, potentially enhancing the impact of RT on tumor recurrence. This study investigated the ability of FG to incorporate and release, in non-degraded form, the radiation sensitizers 5-Fluorouracil (5FU) and Motexafin gadolinium (MGd). METHODS: FG layers were created in a 24-well plate by combining thrombin, fibrinogen, and 5FU or MGd. Supernatants from these layers were collected at various intervals and added to F98 glioma spheroid cultures in 96-well plates. Radiation was applied either before or after RS application as single or fractionated dosages. Spheroid growth was monitored for 14 days. RESULTS: Combined treatment of FG-released 5FU and RT significantly inhibited spheroid growth compared to RS or RT as a single treatment. As a free drug, MGd demonstrated its efficacy in reducing spheroid volume, but had diminished potency as a released RS. Fractionated radiation was more effective than single dose radiation. CONCLUSION: Non-degraded RS was released from the FG for up to 72 h. FG-released 5FU greatly increased the efficacy of radiation therapy.

Photon-Momentum-Enabled Electronic Raman Scattering in Silicon Glass

(2024)

The nature of enhanced photoemission in disordered and amorphous solids is an intriguing question. A point in case is light emission in porous and nanostructured silicon, a phenomenon that is still not fully understood. In this work, we study structural photoemission in heterogeneous cross-linked silicon glass, a material that represents an intermediate state between the amorphous and crystalline phases, characterized by a narrow distribution of structure sizes. This model system shows a clear dependence of photoemission on size and disorder across a broad range of energies. While phonon-assisted indirect optical transitions are insufficient to describe observable emissions, our experiments suggest these can be understood through electronic Raman scattering instead. This phenomenon, which is not commonly observed in crystalline semiconductors, is driven by structural disorder. We attribute photoemission in this disordered system to the presence of an excess electron density of states within the forbidden gap (Urbach bridge) where electrons occupy trapped states. Transitions from gap states to the conduction band are facilitated through electron-photon momentum matching, which resembles Compton scattering but is observed for visible light and driven by the enhanced momentum of a photon confined within the nanostructured domains. We interpret the light emission in structured silicon glass as resulting from electronic Raman scattering. These findings emphasize the role of photon momentum in the optical response of solids that display disorder on the nanoscale.

Noninvasive Imaging Techniques for Monitoring Cellular Response to Treatment in Stable Vitiligo

(2024)

Shining Light in Mechanobiology: Optical Tweezers, Scissors, and Beyond

(2024)

Mechanobiology helps us to decipher cell and tissue functions by looking at changes in their mechanical properties that contribute to development, cell differentiation, physiology, and disease. Mechanobiology sits at the interface of biology, physics and engineering. One of the key technologies that enables characterization of properties of cells and tissue is microscopy. Combining microscopy with other quantitative measurement techniques such as optical tweezers and scissors, gives a very powerful tool for unraveling the intricacies of mechanobiology enabling measurement of forces, torques and displacements at play. We review the field of some light based studies of mechanobiology and optical detection of signal transduction ranging from optical micromanipulation─optical tweezers and scissors, advanced fluorescence techniques and optogenentics. In the current perspective paper, we concentrate our efforts on elucidating interesting measurements of forces, torques, positions, viscoelastic properties, and optogenetics inside and outside a cell attained when using structured light in combination with optical tweezers and scissors. We give perspective on the field concentrating on the use of structured light in imaging in combination with tweezers and scissors pointing out how novel developments in quantum imaging in combination with tweezers and scissors can bring to this fast growing field.

Cover page of Current clinical evidence is insufficient to support HMME–PDT as the first choice of treatment for young children with port wine birthmarks

Current clinical evidence is insufficient to support HMME–PDT as the first choice of treatment for young children with port wine birthmarks

(2024)

Background

Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades.

Aim

To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities.

Method

PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C₀ ), with data weighted by cohort size, was used to evaluate the final efficacy for each modality.

Result

A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C₀ , 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C₀ , 0.54 vs. 0.46, p = 0.714), and young children (C₀ , 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults.

Conclusion

PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Hybrid-supervised deep learning for domain transfer 3D protoacoustic image reconstruction.

(2024)

Objective

Protoacoustic imaging showed great promise in providing real-time 3D dose verification of proton therapy. However, the limited acquisition angle in protoacoustic imaging induces severe artifacts, which impairs its accuracy for dose verification. In this study, we developed a hybrid-supervised deep learning method for protoacoustic imaging to address the limited view issue. Approach: We proposed a Recon-Enhance two-stage deep learning method. In the Recon-stage, a transformer-based network was developed to reconstruct initial pressure maps from raw acoustic signals. The network is trained in a hybrid-supervised approach, where it is first trained using supervision by the iteratively reconstructed pressure map and then fine-tuned using transfer learning and self-supervision based on the data fidelity constraint. In the Enhance-stage, a 3D U-net is applied to further enhance the image quality with supervision from the ground truth pressure map. The final protoacoustic images are then converted to dose for proton verification. Main results: The results evaluated on a dataset of 126 prostate cancer patients achieved an average root mean squared errors (RMSE) of 0.0292, and an average structural similarity index measure (SSIM) of 0.9618. Qualitative results also demonstrated that our approach addressed the limit-view issue. Dose verification achieved an average RMSE of 0.018, and an average SSIM of 0.9891. Gamma index evaluation demonstrated a high agreement (94.7% and 95.7% for 1%/3 mm and 1%/5 mm) between the predicted and the ground truth dose maps. The processing time was reduced to 6 seconds, demonstrating its feasibility for online 3D dose verification for prostate proton therapy. Significance: Our study achieved start-of-the-art performance in the challenging task of direct reconstruction from radiofrequency signals, demonstrating the great promise of PA imaging as a highly efficient and accurate tool for in-vivo 3D proton dose verification to minimize the range uncertainties of proton therapy to improve its precision and outcomes. .

Method for producing identical spectral copies of ultra-broadband arbitrary light fields

(2024)

An ultra-broadband beam splitter arrangement, with a spectral amplitude response that is over seven orders-of-magnitude more uniform than broadband, multi-layer dielectric beam splitters, can be created by the combination of multiple Fresnel events on an uncoated, optical flat when used at a specific angle-of-incidence. This beam splitter arrangement produces three, spectral copies of the original, two of which have identical spectral phase. In this manuscript we derive the precise angle at which this maximally flat spectral amplitude response occurs for any material and present this angle’s material and polarization dependence.

Long-range optical coherence tomography of pediatric airway during drug induced sleep endoscopy: A preliminary report

(2024)

Objective

Drug induced sleep endoscopy (DISE) is often performed for pediatric obstructive sleep apnea (OSA) when initial diagnostic studies do not provide adequate information for therapy. However, DISE scoring is subjective and with limitations. This proof-of-concept study demonstrates the use of a novel long-range optical coherence tomography (LR-OCT) system during DISE of two pediatric patients.

Methods

LR-OCT was used to visualize the airway of pediatric patients during DISE. At the conclusion of DISE, the OCT probe was guided in the airway under endoscopic visual guidance, and cross-sectional images were acquired at the four VOTE locations. Data processing involved image resizing and alignment, followed by rendering of three-dimensional (3D) volumetric models of the airways.

Results

Two patients were included in this study. Patient one had 18.4%, 20.9%, 72.3%, and 97.3% maximal obstruction at velum, oropharynx, tongue base, and epiglottis, while patient two had 40.2%, 41.4%, 8.0%, and 17.5% maximal obstruction at these regions, respectively. Three-dimensional reconstructions of patients' airways were also constructed from the OCT images.

Conclusion

This proof-of-concept study demonstrates the successful evaluation of pediatric airway during DISE using LR-OCT, which accurately identified sites and degrees of obstruction with respective 3D airway reconstruction.

Cosmetic Directors on ACGME Program Requirements: A Cross-Sectional Survey

(2024)

Female genital mutilation: Overview and dermatologic relevance.

(2024)

Female genital mutilation (FGM) is a common cultural practice, which involves the partial or complete removal of the external female genitalia. With increasing immigration from regions where the practice is endemic, there has been a growing prevalence of FGM in the United States and other developed nations. However, most medical professionals lack the baseline knowledge regarding FGM and its associated health complications. Given this increasing trend, dermatologists should anticipate an increasing number of patients with a history of FGM in their practice. While some of the obstetric, gynecologic, and psychologic consequences of FGM have been well-reported, the dermatologic findings are less characterized. Thus, this review article aims to provide dermatologists with a fundamental understanding of the prevalence, cultural significance, and health implications of FGM with a focus on the associated dermatological findings and provides recommendations on how dermatologists can address this sensitive matter.

Beckman Laser Institute & Medical Clinic