Enhanced porphyrin-based hypoxia imaging by temporal oversampling of delayed fluorescence signal.

Significance: Protoporphyrin IX (PpIX) delayed fluorescence (DF) is inversely related to the oxygen present in tissues and has potential as a novel biomarker for surgical guidance and real-time tissue metabolism assessment. Despite the unique promise of this technique, its successful clinical translation is limited by the low intensity emitted.

Aim: We developed a systematic study of ways to increase the PpIX DF signal through acquisition sampling changes, allowing optimized imaging at video rates.

AAPM Task Group Report 274: Fluence rate dosimetry for photodynamic therapy (PDT).

Photodynamic therapy (PDT) is a treatment modality clinically approved for several oncologic indications, including esophageal and endobronchial cancers, precancerous conditions including Barrett's esophagus and actinic keratosis, and benign conditions like age-related macular degeneration. While it is currently clinically underused, PDT is an area of significant research interest. Because PDT relies on the absorption of light energy by intrinsic or administered absorbers, the dosimetric quantity of interest is the absorbed energy per unit mass of tissue, proportional to the fluence rate of light in tissue.

Pulse Oximetry: 50 Years of Inventions & Discoveries in Biomedical Optics.

The editorial introduces the JBO Special Issue on Pulse Oximetry.

First-in-human Study of ABY-029, a Novel Fluorescent Peptide that Targets Epidermal Growth Factor Receptor, Applied to Soft-Tissue Sarcomas.

ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies.

Combined dual-channel fluorescence depth sensing of indocyanine green and protoporphyrin IX kinetics in subcutaneous murine tumors.

Significance: Fluorescence sensing within tissue is an effective tool for tissue characterization; however, the modality and geometry of the image acquisition can alter the observed signal.

Aim: We introduce a novel optical fiber-based system capable of measuring two fluorescent contrast agents through 2 cm of tissue with simple passive electronic switching between the excitation light, simultaneously acquiring fluorescence and excitation data. The goal was to quantify indocyanine green (ICG) and protoporphyrin IX (PpIX) within tissue, and the sampling method was compared with wide-field surface imaging to contrast the value of deep sensing versus surface imaging.

Optimized scintillation imaging in low dose rate and bright room light conditions.

. To develop a robust method for non-contact surface dosimetry during Total Body Irradiation (TBI) that uses an optimally paired choice of scintillator material with camera photocathode and can work insensitively to the normal ambient room lighting conditions (∼500 Lux)..

Major contributors to FLASH sparing efficacy emerge from murine skin studies: dose rate, total dose per fraction, anesthesia and oxygenation.

Background: Normal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect with an equivalent tumor response, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected.

Methods: This study reviews the status of the field, focusing on the proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect.

Results: Murine studies have largely focused on acute damage responses, developing over 3-8 weeks, to single doses of FLASH versus conventional dose rate (CDR), suggesting that at dose rates above tens of Gray per second, with a total dose of more than 20 Gy, the FLASH effect is induced.

Noise & mottle suppression methods for cumulative Cherenkov images of radiation therapy delivery.

Cherenkov imaging during radiotherapy provides a real time visualization of beam delivery on patient tissue, which can be used dynamically for incident detection or to review a summary of the delivered surface signal for treatment verification. Very few photons form the images, and one limitation is that the noise level per frame can be quite high, and mottle in the cumulative processed images can cause mild overall noise. This work focused on removing or suppressing noise via image postprocessing.

Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods And Materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator.

MRI-guided Near-infrared Spectroscopic Tomography (MRg-NIRST) Imaging System with Wearable Breast Optical Interface for Breast Cancer Imaging.

To develop a novel Magnetic Resonance Imaging (MRI)-guided Near-Infrared Spectroscopic Tomography (MRg-NIRST) imaging system with an MRI-compatible breast optical interface for breast imaging.

Robust Real-time Segmentation of Bio-Morphological Features in Human Cherenkov Imaging during Radiotherapy via Deep Learning.

Cherenkov imaging enables real-time visualization of megavoltage X-ray or electron beam delivery to the patient during Radiation Therapy (RT). Bio-morphological features, such as vasculature, seen in these images are patient-specific signatures that can be used for verification of positioning and motion management that are essential to precise RT treatment. However until now, no concerted analysis of this biological feature-based tracking was utilized because of the slow speed and accuracy of conventional image processing for feature segmentation.

Dynamic oxygen assessment techniques enable determination of anesthesia's impact on tissue.

Tissue oxygenation is well understood to impact radiosensitivity, with reports demonstrating a significant effect of breathing condition and anesthesia type on tissue oxygenation levels and radiobiological response. However, the temporal kinetics of intracellular and extracellular oxygenation have never been quantified, on the timescale that may affect radiotherapy studies. C57BL/6 mice were anesthetized using isoflurane at various percentages or ketamine/xylazine (ket/xyl: 100/10 mg/kg) (N = 48).

The United States Department of Energy and National Institutes of Health Collaboration: Medical Care Advances by Discovery in Radiation Detection.

A National Institutes of Health (NIH) and U.S. Department of Energy (DOE) Office of Science virtual workshop on shared general topics was held in July of 2021 and reported on in this publication in January of 2023.

Onward to Better Surgery - the Critical Need for Improved Ex Vivo Testing and Training Methods.

Guided surgery has demonstrated significant improvements in patient outcomes in some disease processes. Interest in this field has led to substantial growth in the technologies under investigation. Most likely no single technology will prove to be "best," and combinations of macro- and microscale guidance-using radiological imaging navigation, probes (activatable, perfusion, and molecular-targeted; large- and small-molecule), autofluorescence, tissue intrinsic optical properties, bioimpedance, and other characteristics-will offer patients and surgeons the greatest opportunity for high-success/low-morbidity medical interventions.

Commissioning an ultra-high-dose-rate electron linac with end-to-end tests.

. The FLASH effect can potentially be used to improve the therapeutic ratio of radiotherapy (RT) through delivery of Ultra-high-dose-rate (UHDR) irradiation. Research is actively being conducted to translate UHDR-RT and for this purpose the Mobetron is capable of producing electron beams at both UHDR and conventional dose rates for FLASH research and translation.

Impact of signal-to-noise ratio and contrast definition on the sensitivity assessment and benchmarking of fluorescence molecular imaging systems.

Significance: Standardization of fluorescence molecular imaging (FMI) is critical for ensuring quality control in guiding surgical procedures. To accurately evaluate system performance, two metrics, the signal-to-noise ratio (SNR) and contrast, are widely employed. However, there is currently no consensus on how these metrics can be computed.

Electron beam response corrections for an ultra-high-dose-rate capable diode dosimeter.

Background: Ultra-high-dose-rate (UHDR) electron beams have been commonly utilized in FLASH studies and the translation of FLASH Radiotherapy (RT) to the clinic. The EDGE diode detector has potential use for UHDR dosimetry albeit with a beam energy dependency observed.

Purpose: The purpose is to present the electron beam response for an EDGE detector in dependence on beam energy, to characterize the EDGE detector's response under UHDR conditions, and to validate correction factors derived from the first detailed Monte Carlo model of the EDGE diode against measurements, particularly under UHDR conditions.

Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.

Significance: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries.

Aim: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples.

Approach: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed.

Anesthetic Oxygen Use and Sex Are Critical Factors in the FLASH Sparing Effect.

Purpose: Ultra High Dose-Rate (UHDR) radiation has been reported to spare normal tissue, compared with Conventional Dose-Rate (CDR) radiation. However, important work remains to be done to improve the reproducibility of the FLASH effect. A better understanding of the biologic factors that modulate the FLASH effect may shed light on the mechanism of FLASH sparing.

Intracellular Oxygen Transient Quantification in Vivo During Ultra-High Dose Rate FLASH Radiation Therapy.

Purpose: Large, rapid extracellular oxygen transients (ΔpO) have been measured in vivo during ultra-high dose rate radiation therapy; however, it has been unclear if they match intracellular oxygen levels. Here, the endogenously produced protoporphyrin IX (PpIX) delayed fluorescence signal was measured as an intracellular in-vivo oxygen sensor to quantify these transients, with direct comparison to extracellular pO. Intracellular ΔpO is closer to the cellular DNA, the site of major radiobiological damage, and therefore should help elucidate radiochemical mechanisms of the FLASH effect and potentially be translated to human tissue measurement.

Time-gated single-pixel imaging of Cherenkov emission from a medical linear accelerator.

Cherenkov imaging is an ideal tool for real-time in vivo verification of a radiation therapy dose. Given that radiation is pulsed from a medical linear accelerator (LINAC) together with weak Cherenkov emissions, time-gated high-sensitivity imaging is required for robust measurements. Instead of using an expensive camera system with limited efficiency of detection in each pixel, a single-pixel imaging (SPI) approach that maintains promising sensitivity over the entire spectral band could be used to provide a low-cost and viable alternative.

Technical note: Visual, rapid, scintillation point dosimetry for in vivo MV photon beam radiotherapy treatments.

Background: While careful planning and pre-treatment checks are performed to ensure patient safety during external beam radiation therapy (EBRT), inevitable daily variations mean that in vivo dosimetry (IVD) is the only way to attain the true delivered dose. Several countries outside the US require daily IVD for quality assurance. However, elsewhere, the manual labor and time considerations of traditional in vivo dosimeters may be preventing frequent use of IVD in the clinic.

Rapid Switching of a C-Series Linear Accelerator Between Conventional and Ultrahigh-Dose-Rate Research Mode With Beamline Modifications and Output Stabilization.

Purpose: In this study, a C-series linear accelerator was configured to enable rapid and reliable conversion between the production of conventional electron beams and an ultrahigh-dose-rate (UHDR) electron beamline to the treatment room isocenter for FLASH radiation therapy. Efforts to tune the beam resulted in a consistent, stable UHDR beamline.

Methods And Materials: The linear accelerator was configured to allow for efficient switching between conventional and modified electron output modes within 2 minutes.