Safety and Feasibility of Photodynamic Therapy for Percutaneous Image-guided Abdominopelvic Abscess Drainage: Phase 1 Trial.

Background Standard-of-care abscess management includes image-guided percutaneous drainage and antibiotics; however, cure rates vary, and concern for antibiotic-resistant bacteria is growing. Photodynamic therapy (PDT), which uses light-activated dyes to generate cytotoxic reactive oxygen species, could complement the standard of care by sterilizing the abscess at the time of drainage. Purpose To evaluate safety and feasibility of PDT with methylene blue (hereafter, MB-PDT) at the time of percutaneous abscess drainage. Materials and Methods This prospective, open-label, dose-escalation, first-in-humans, registered phase 1 clinical study of MB-PDT included participants who underwent percutaneous abdominal or pelvic abscess drainage with CT or US guidance from January 2015 to March 2020 and September 2022 to September 2023. Following drainage, MB-PDT was performed with laser illumination at a fluence rate of 20 mW/cm2, with fluence groups of 6, 12, 18, 24, 30, and 36 J/cm2 (n = 3 each). The primary outcome was safety, indicated by absence of fat embolism, MB escape, abscess wall damage, and need for surgery to remove optical fibers. Preliminary efficacy end points included the time to drainage catheter removal, drainage catheter output volume, and clinical symptom and fever duration. Relationships between fluence and outcomes were analyzed with Spearman correlation and linear regression analyses, and ordinary one-way analysis of variance was used for group comparisons. Results MB-PDT was safe and feasible in all 18 participants (mean age, 60.1 years ± 18.3 [SD]; 10 female), with no negative safety outcomes observed for any participant. No study-related adverse events were encountered, and the procedure did not increase reported pain (P = .1). Clinical symptom and fever duration was shorter in participants receiving higher fluences (30 and 36 J/cm2 vs 6 J/cm2) (P = .03). The presence of antibiotic-resistant bacteria was not predictive of clinical symptom and fever duration (ß = 0.13, P = .37). Conclusion MB-PDT was a safe and feasible adjunct to image-guided percutaneous abscess drainage. Clinical measures indicated a dose-dependent response to PDT. ClinicalTrials.gov registration no.: NCT02240498 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Johnston and Goldberg in this issue.

Breast Ultrasound Volume Sweep Imaging: A New Horizon in Expanding Imaging Access for Breast Cancer Detection.

OBJECTIVE: The majority of people in the world lack basic access to breast diagnostic imaging resulting in delay to diagnosis of breast cancer. In this study, we tested a volume sweep imaging (VSI) ultrasound protocol for evaluation of palpable breast lumps that can be performed by operators after minimal training without prior ultrasound experience as a means to increase accessibility to breast ultrasound. METHODS: Medical students without prior ultrasound experience were trained for less than 2 hours on the VSI breast ultrasound protocol. Patients presenting with palpable breast lumps for standard of care ultrasound examination were scanned by a trained medical student with the VSI protocol using a Butterfly iQ handheld ultrasound probe. Video clips of the VSI scan imaging were later interpreted by an attending breast imager. Results of VSI scan interpretation were compared to the same-day standard of care ultrasound examination. RESULTS: Medical students scanned 170 palpable lumps with the VSI protocol. There was 97% sensitivity and 100% specificity for a breast mass on VSI corresponding to 97.6% agreement with standard of care (Cohen's κ = 0.95, P < .0001). There was a detection rate of 100% for all cancer presenting as a sonographic mass. High agreement for mass characteristics between VSI and standard of care was observed, including 87% agreement on Breast Imaging-Reporting and Data System assessments (Cohen's κ = 0.82, P < .0001). CONCLUSIONS: Breast ultrasound VSI for palpable lumps offers a promising means to increase access to diagnostic imaging in underserved areas. This approach could decrease delay to diagnosis for breast cancer, potentially improving morbidity and mortality.

Ovarian Cancer Detection in Average-Risk Women: Classic- versus Nonclassic-appearing Adnexal Lesions at US.

Background Several US risk stratification schemas for assessing adnexal lesions exist. These multiple-subcategory systems may be more multifaceted than necessary for isolated adnexal lesions in average-risk women. Purpose To explore whether a US-based classification scheme of classic versus nonclassic appearance can be used to help appropriately triage women at average risk of ovarian cancer without compromising diagnostic performance. Materials and Methods This retrospective multicenter study included isolated ovarian lesions identified at pelvic US performed between January 2011 and June 2014, reviewed between September 2019 and September 2020. Lesions were considered isolated in the absence of ascites or peritoneal implants. Lesions were classified as classic or nonclassic based on sonographic appearance. Classic lesions included simple cysts, hemorrhagic cysts, endometriomas, and dermoids. Otherwise, lesions were considered nonclassic. Outcomes based on histopathologic results or clinical or imaging follow-up were recorded. Diagnostic performance and frequency of malignancy were calculated. Frequency of malignancy between age groups was compared using the χ2 test, and Poisson regression was used to explore relationships between imaging features and malignancy. Results A total of 970 isolated lesions in 878 women (mean age, 42 years ± 14 [SD]) were included. The malignancy rate for classic lesions was less than 1%. Of 970 lesions, 53 (6%) were malignant. The malignancy rate for nonclassic lesions was 32% (33 of 103) when blood flow was present and 8% (16 of 194) without blood flow (P < .001). For women older than 60 years, the malignancy rate was 50% (10 of 20 lesions) when blood flow was present and 13% (five of 38) without blood flow (P = .004). The sensitivity, specificity, positive predictive value, and negative predictive value of the classic-versus-nonclassic schema was 93% (49 of 53 lesions), 73% (669 of 917 lesions), 17% (49 of 297 lesions), and 99% (669 of 673 lesions), respectively, for detection of malignancy. Conclusion Using a US classification schema of classic- or nonclassic-appearing adnexal lesions resulted in high sensitivity and specificity in the diagnosis of malignancy in ovarian cancer. The highest risk of cancer was in isolated nonclassic lesions with blood flow in women older than 60 years. © RSNA, 2022 See also the editorial by Baumgarten in this issue.

Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training.

A major challenge in the cognitive training field is inducing broad, far-transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision-based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non-learners) and a subset of participants in the MLA (i.e., MLA non-learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.

Rethinking Time-to-Exchange: Outcomes of Nephrostomy Tube Placement in Pregnancy.

This study evaluated outcomes for percutaneous nephrostomy tube placement in pregnant patients, including potential complications that required early, unplanned tube exchange. A retrospective review was conducted for 51 pregnant patients and a nonpregnant cohort matched 1:1 who received percutaneous nephrostomy tube placement between 2012 and 2020. Factors potentially contributing to unplanned tube exchanges were analyzed, including gestational age, prevalence and severity of hydronephrosis, presence of renal calculi, and serum calcium level. The mean tube exchange interval was significantly shorter in the pregnant group (3.4 weeks ± 1.8 [standard deviation] vs 5.7 weeks ± 0.7, P < .0001), and pregnant subjects were significantly more likely to require reintervention before the 6-week scheduled exchange (80.4% vs 21.6%, P < .0001). The serum calcium level was lower in pregnant subjects (8.4 mg/dL ± 0.4 vs 8.9 mg/dL ± 0.7, P = .002). A shorter interval schedule (every 3 weeks) of routine percutaneous nephrostomy tube exchange in pregnant patients may be necessary to avoid complications.

Testing telediagnostic obstetric ultrasound in Peru: a new horizon in expanding access to prenatal ultrasound.

BACKGROUND: Ninety-four percent of all maternal deaths occur in low- and middle-income countries, and the majority are preventable. Access to quality Obstetric ultrasound can identify some complications leading to maternal and neonatal/perinatal mortality or morbidity and may allow timely referral to higher-resource centers. However, there are significant global inequalities in access to imaging and many challenges to deploying ultrasound to rural areas. In this study, we tested a novel, innovative Obstetric telediagnostic ultrasound system in which the imaging acquisitions are obtained by an operator without prior ultrasound experience using simple scan protocols based only on external body landmarks and uploaded using low-bandwidth internet for asynchronous remote interpretation by an off-site specialist. METHODS: This is a single-center pilot study. A nurse and care technician underwent 8 h of training on the telediagnostic system. Subsequently, 126 patients (68 second trimester and 58 third trimester) were recruited at a health center in Lima, Peru and scanned by these ultrasound-naïve operators. The imaging acquisitions were uploaded by the telemedicine platform and interpreted remotely in the United States. Comparison of telediagnostic imaging was made to a concurrently performed standard of care ultrasound obtained and interpreted by an experienced attending radiologist. Cohen's Kappa was used to test agreement between categorical variables. Intraclass correlation and Bland-Altman plots were used to test agreement between continuous variables. RESULTS: Obstetric ultrasound telediagnosis showed excellent agreement with standard of care ultrasound allowing the identification of number of fetuses (100% agreement), fetal presentation (95.8% agreement, κ =0.78 (p < 0.0001)), placental location (85.6% agreement, κ =0.74 (p < 0.0001)), and assessment of normal/abnormal amniotic fluid volume (99.2% agreement) with sensitivity and specificity > 95% for all variables. Intraclass correlation was good or excellent for all fetal biometric measurements (0.81-0.95). The majority (88.5%) of second trimester ultrasound exam biometry measurements produced dating within 14 days of standard of care ultrasound. CONCLUSION: This Obstetric ultrasound telediagnostic system is a promising means to increase access to diagnostic Obstetric ultrasound in low-resource settings. The telediagnostic system demonstrated excellent agreement with standard of care ultrasound. Fetal biometric measurements were acceptable for use in the detection of gross discrepancies in fetal size requiring further follow up.

New Ultrasound Telediagnostic System for Low-Resource Areas: Pilot Results From Peru.

Billions of people around the world lack access to diagnostic imaging. To address this issue, we piloted a comprehensive ultrasound telediagnostic system, which uses ultrasound volume sweep imaging (VSI) acquisitions capable of being performed by operators without prior traditional ultrasound training and new telemedicine software capable of sending imaging acquisitions asynchronously over low Internet bandwidth for remote interpretation. The telediagnostic system was tested with obstetric, right upper quadrant abdominal, and thyroid volume sweep imaging protocols in Peru. Scans obtained by operators without prior ultrasound experience were sent for remote interpretation by specialists using the telemedicine platform. Scans obtained allowed visualization of the target region in 96% of cases with diagnostic imaging quality. This telediagnostic system shows promise in improving health care disparities in the developing world.

Longitudinal Functional Brain Mapping in Supernormals.

Prevention of age-related cognitive decline is an increasingly important topic. Recently, increased attention is being directed at understanding biological models of successful cognitive aging. Here, we examined resting-state brain regional low-frequency oscillations using functional magnetic resonance imaging in 19 older adults with excellent cognitive abilities (Supernormals), 28 older adults with normative cognition, 57 older adults with amnestic mild cognitive impairment, and 26 with Alzheimer's disease. We identified a "Supernormal map", a set of regions whose oscillations were resistant to the aging-associated neurodegenerative process, including the right fusiform gyrus, right middle frontal gyrus, right anterior cingulate cortex, left middle temporal gyrus, left precentral gyrus, and left orbitofrontal cortex. The map was unique to the Supernormals, differentiated this group from cognitive average-ager comparisons, and predicted a 1-year change in global cognition (indexed by the Montreal Cognitive Assessment scores, adjusted R2 = 0.68). The map was also correlated to Alzheimer's pathophysiological features (beta-amyloid/pTau ratio, adjusted R2 = 0.66) in participants with and without cognitive impairment. These findings in phenotypically successful cognitive agers suggest a divergent pattern of brain regions that may either reflect inherent neural integrity that contributes to Supernormals' cognitive success, or alternatively indicate adaptive reorganization to the demands of aging.

Photofrin® photodynamic therapy with intratumor photosensitizer injection provides similar tumor response while reducing systemic skin photosensitivity: Pilot murine study.

OBJECTIVES: The goal of this study was to compare tumor response to Photofrin® photodynamic therapy using intravenous and intratumoral injection of photosensitizer. Systemic skin photosensitivity and photosensitizer distribution were also compared between the two delivery methods. METHODS: SCCVII tumors were initiated in the hind legs of female C3H mice and grown to a volume of ∼1,000 mm3 . Photofrin® was delivered intravenously via the tail vein at a concentration of 2 mg/kg or intratumorally at concentrations ranging from 0.5-2 mg/kg. A 630 nm laser illumination was delivered via interstitial diffuser placement at a fluence rate of 400 mW/cm and fluence of 100 J/cm. Mice were maintained under normal room lighting for 24 hours after treatment, at which point photographs were captured for assessment of skin photosensitivity. Animals were then sacrificed, and their tumors were excised, sectioned, imaged, and stained with hematoxylin and eosin (H&E). H&E slides were imaged to assess necrosis post-PDT, and skin photographs were evaluated by two blinded reviewers for quantification of skin photosensitivity. Whole-body fluorescence imaging was performed before and after photodynamic therapy. RESULTS: Tumor necrosis was not significantly different based on treatment group (P = 0.33), while skin photosensitivity was significantly reduced in animals that received Photofrin® intratumorally (P = 0.0005). Fluorescence imaging revealed similar photosensitizer fluorescence in excised tumors for intratumor and intravenous injection of Photofrin® (P = 0.48), although fluorescence decreased significantly with decreasing intratumor injection concentration (P= 0.01). CONCLUSIONS: This pilot study shows that intratumoral administration of Photofrin® has the potential to produce similar tumor outcomes, while reducing systemic skin photosensitivity. Further studies are warranted to characterize and optimize intratumor delivery. Lasers Surg. 50:476-482, 2018. © 2017 Wiley Periodicals, Inc.

Long-Term Patency of Arteriovenous Fistulae Salvaged by Balloon Angioplasty with and without Accessory Vein Embolization: A Retrospective Study.

PURPOSE: To investigate whether accessory vein embolization (AVE) improves long-term performance of salvaged nonmaturing arteriovenous fistulae (AVFs). MATERIALS AND METHODS: This retrospective review included 72 patients who underwent percutaneous balloon angioplasty for salvage of nonmaturing AVFs between 2008 and 2014. AVE was performed on 32 patients between 2008 and 2011 (mean age, 59 y [range, 33-85 y]; men, n = 21; women, n = 11; upper arm, n = 17; forearm, n = 15), whereas the procedure was not performed on 40 patients after 2011 (mean age, 62 y [range, 28-85 y]; men, n = 26; women, n = 14; upper arm, n = 26; forearm, n = 14). Endpoints compared between groups included number of procedures required to achieve maturation, time to maturation, number of procedures required to maintain patency, and duration of primary and secondary patency after intervention. RESULTS: There was no statistically significant difference in number of procedures to achieve maturation (2.1 ± 1.4 vs 2.4 ± 1.2; P = .24) or time to maturation (26.1 d ± 56.2 vs 41.1 d ± 54.6; P = .072) between AVE and no embolization groups. Primary (P = .21) and secondary patency (P = .14) after intervention were not significantly different between groups. The number of procedures performed to maintain patency after maturation was significantly greater in the AVE group for patients with forearm AVFs (0.11 ± 0.098 vs 0.04 ± 0.064 per patient year; P = .039) but not for patients with upper arm AVFs. CONCLUSIONS: AVE of AVFs after balloon angioplasty does not lead to significantly improved long-term outcomes. Percutaneous salvage of nonmaturing AVFs in the forearm without AVE resulted in a decreased number of interventions to maintain patency.

Application of transfer learning for rapid calibration of spatially resolved diffuse reflectance probes for extraction of tissue optical properties.

Significance: Treatment planning for light-based therapies including photodynamic therapy requires tissue optical property knowledge. This is recoverable with spatially resolved diffuse reflectance spectroscopy (DRS) but requires precise source-detector separation (SDS) determination and time-consuming simulations. Aim: An artificial neural network (ANN) to map from DRS at multiple SDS to optical properties was created. This trained ANN was adapted to fiber-optic probes with varying SDS using transfer learning (TL). Approach: An ANN mapping from measurements to Monte Carlo simulation to optical properties was created with one fiber-optic probe. A second probe with different SDS was used for TL algorithm creation. Data from a third were used to test this algorithm. Results: The initial ANN recovered absorber concentration with RMSE=0.29 µM (7.5% mean error) and µs' at 665 nm (µs,665') with RMSE=0.77 cm-1 (2.5% mean error). For probe 2, TL significantly improved absorber concentration (0.38 versus 1.67 µM RMSE, p=0.0005) and µ's,665 (0.71 versus 1.8 cm-1 RMSE, p=0.0005) recovery. A third probe also showed improved absorber (0.7 versus 4.1 µM RMSE, p<0.0001) and µs,665' (1.68 versus 2.08 cm-1 RMSE, p=0.2) recovery. Conclusions: TL-based probe-to-probe calibration can rapidly adapt an ANN created for one probe to similar target probes, enabling accurate optical property recovery with the target probe.

First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy by in vivo diffuse reflectance spectroscopy.

Significance: Efficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects. Aim: The objective was to extract optical properties and photosensitizer concentration from spatially resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a phase 1 clinical trial. Approach: Diffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties. Results: Pre-MB abscess wall absorption coefficients at 665 nm were 0.15±0.1 cm-1 (0.03 to 0.36 cm-1) and 10.74±15.81 cm-1 (0.08 to 49.3 cm-1) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm-1 (4.8 to 13.2 cm-1) and 5.6±2.26 cm-1 (1.6 to 9.9 cm-1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83%±35.78% (5.6% to 100%) pre-MB and 36.29%±25.1% (0.0001% to 76.4%) post-MB. Determined MB concentrations were 71.83±108.22 µM (0 to 311 µM). Conclusions: We observed substantial inter-subject variation in both native wall optical properties and MB uptake. This underscores the importance of making these measurements for patient-specific treatment planning.

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination.

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm-2(92% versus 38%,p= 0.01) and 20 mW cm-2(62% versus 15%,p= 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm-2target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm-2target was significantly correlated with measured abscess wall absorption (ρ= 0.7,p= 0.008), but not abscess surface area (ρ= 0.2,p= 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p= 0.0005) and required laser power (p= 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm-2target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as 'Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,' with ClinicalTrials.gov identifier NCT02240498).

Impact of Early Direct Patient Notification on Follow-Up Completion for Nonurgent Actionable Incidental Radiologic Findings.

PURPOSE: The aim of this study was to evaluate whether early direct patient notification in addition to an existing multistage recommendation-tracking system (Backstop) increases follow-up completion rates for actionable incidental findings (AIFs). Patient attitudes toward early notification were also assessed. METHODS: This prospective, randomized controlled trial recruited patients with AIFs requiring follow-up being enrolled into the Backstop system. Patients were randomized into four groups: those receiving additional early direct notification in a mailed letter (group 1, similar to Pennsylvania Act 112), by phone (group 2), or in an electronic portal message (group 3) and a control group (group 4) without additional notifications added to the existing Backstop system. Differences in follow-up completion rates among these groups were determined using χ2 tests. Patients were surveyed on binary yes/no and Likert-type scale questions, and descriptive statistics are reported. RESULTS: Data from 2,548 randomized patients were analyzed for the study, including 593 patients notified by letter, 637 notified by phone, 701 notified by portal, and 617 control patients. Group 3 demonstrated the lowest rate of follow-up completion within 1 month of the follow-up due date at 36.4%, compared with 58.7% for group 1, 60.4% for group 2, and 53.2% for group 4 (P < .0001 for all). Group 2 was the only group to have a significantly higher completion rate than group 4 (P = .014). Patients responded positively regarding early notification and preferred electronic portal communication. CONCLUSIONS: Early direct notification had a mixed impact on follow-up completion rates on the basis of communication modality but was positively received by patients and may have health care benefits when implemented within a recommendation-tracking system.

WATUNet: a deep neural network for segmentation of volumetric sweep imaging ultrasound.

Limited access to breast cancer diagnosis globally leads to delayed treatment. Ultrasound, an effective yet underutilized method, requires specialized training for sonographers, which hinders its widespread use. Volume sweep imaging (VSI) is an innovative approach that enables untrained operators to capture high-quality ultrasound images. Combined with deep learning, like convolutional neural networks, it can potentially transform breast cancer diagnosis, enhancing accuracy, saving time and costs, and improving patient outcomes. The widely used UNet architecture, known for medical image segmentation, has limitations, such as vanishing gradients and a lack of multi-scale feature extraction and selective region attention. In this study, we present a novel segmentation model known as Wavelet_Attention_UNet (WATUNet). In this model, we incorporate wavelet gates and attention gates between the encoder and decoder instead of a simple connection to overcome the limitations mentioned, thereby improving model performance. Two datasets are utilized for the analysis: the public 'Breast Ultrasound Images' dataset of 780 images and a private VSI dataset of 3818 images, captured at the University of Rochester by the authors. Both datasets contained segmented lesions categorized into three types: no mass, benign mass, and malignant mass. Our segmentation results show superior performance compared to other deep networks. The proposed algorithm attained a Dice coefficient of 0.94 and an F1 score of 0.94 on the VSI dataset and scored 0.93 and 0.94 on the public dataset, respectively. Moreover, our model significantly outperformed other models in McNemar's test with false discovery rate correction on a 381-image VSI set. The experimental findings demonstrate that the proposed WATUNet model achieves precise segmentation of breast lesions in both standard-of-care and VSI images, surpassing state-of-the-art models. Hence, the model holds considerable promise for assisting in lesion identification, an essential step in the clinical diagnosis of breast lesions.

Recovery of intrinsic fluorescence from single-point interstitial measurements for quantification of doxorubicin concentration.

BACKGROUND AND OBJECTIVE: We developed a method for the recovery of intrinsic fluorescence from single-point measurements in highly scattering and absorbing samples without a priori knowledge of the sample optical properties. The goal of the study was to demonstrate accurate recovery of fluorophore concentration in samples with widely varying background optical properties, while simultaneously recovering the optical properties. MATERIALS AND METHODS: Tissue-simulating phantoms containing doxorubicin, MnTPPS, and Intralipid-20% were created, and fluorescence measurements were performed using a single isotropic probe. The resulting spectra were analyzed using a forward-adjoint fluorescence model in order to recover the fluorophore concentration and background optical properties. RESULTS: We demonstrated recovery of doxorubicin concentration with a mean error of 11.8%. The concentration of the background absorber was recovered with an average error of 23.2% and the scattering spectrum was recovered with a mean error of 19.8%. CONCLUSION: This method will allow for the determination of local concentrations of fluorescent drugs, such as doxorubicin, from minimally invasive fluorescence measurements. This is particularly interesting in the context of transarterial chemoembolization (TACE) treatment of liver cancer.

Application of Transfer Learning for Rapid Calibration of Spatially-resolved Diffuse Reflectance Probes for Extraction of Tissue Optical Properties.

Significance: Treatment planning for light-based therapies including photodynamic therapy requires tissue optical property knowledge. These are recoverable with spatially-resolved diffuse reflectance spectroscopy (DRS), but requires precise source-detector separation (SDS) determination and time-consuming simulations. Aim: An artificial neural network (ANN) to map from DRS at short SDS to optical properties was created. This trained ANN was adapted to fiber-optic probes with varying SDS using transfer learning. Approach: An ANN mapping from measurements to Monte Carlo simulation to optical properties was created with one fiber-optic probe. A second probe with different SDS was used for transfer learning algorithm creation. Data from a third were used to test this algorithm. Results: The initial ANN recovered absorber concentration with RMSE=0.29 µM (7.5% mean error) and µ s ' at 665 nm (µ s,665 ' ) with RMSE=0.77 cm -1 (2.5% mean error). For probe-2, transfer learning significantly improved absorber concentration (0.38 vs. 1.67 µM, p=0.0005) and µ s,665 ' (0.71 vs. 1.8 cm -1 , p=0.0005) recovery. A third probe also showed improved absorber (0.7 vs. 4.1 µM, p<0.0001) and µ s,665 ' (1.68 vs. 2.08 cm -1 , p=0.2) recovery. Conclusions: A data-driven approach to optical property extraction can be used to rapidly calibrate new fiber-optic probes with varying SDS, with as few as three calibration spectra.

Preliminary measurements of optical properties in human abscess cavities prior to methylene blue photodynamic therapy.

As part of our ongoing Phase 1 clinical trial to establish the safety and feasibility of methylene blue photodynamic therapy (MB-PDT) for human deep tissue abscess cavities, we have shown that determination of abscess wall optical properties is vital for the design of personalized treatment plans aiming to optimize light dose. To that end, we have developed and validated an optical spectroscopy system for the assessment of optical properties at the cavity wall, including a compact fiber-optic probe that can be inserted through the catheter used for the standard of care abscess drainage. Here we report preliminary findings from the first three human subjects to receive these optical spectroscopy measurements. We observed wide variability in concentrations of oxy- and deoxy-hemoglobin prior to MB administration, ranging from 7.3-213 µM and 0.1-47.2 µM, respectively. Reduced scattering coefficients also showed inter-patient variability, but recovered values were more similar between subjects (5.5-10.9 cm-1 at 665 nm). Further, methylene blue uptake was found to vary between subjects, and was associated with a reduction in oxygen saturation. These measured optical properties, along with pre-procedure computed tomography (CT) images, will be used with our previously developed Monte Carlo simulation framework to generate personalized treatment plans for individual patients, which could significantly improve the efficacy of MB-PDT while ensuring safety.

Methylene blue photodynamic therapy of bacterial species found in human abscesses: Planktonic, biofilm, and 3D silicone models.

Deep tissue abscesses are inflammatory, purulent lesions encased in a fibrin-rich pseudocapsule that include multiple bacterial and fungal species. We have initiated a Phase 1 clinical trial exploring the safety and feasibility of methylene blue photodynamic therapy (MB-PDT) at the time of abscess drainage. To optimize treatment parameters for future clinical applications, our goal is to generate physically accurate three-dimensional (3D) abscess models upon which bacteria can be grown. Here, we report results of MB-PDT against four representative bacterial species found in human abscesses in planktonic culture, as biofilms on silicone, and pilot results in 3D silicone molds derived from human abscess computed tomography (CT) images. In all cases, MB-PDT was performed with 665 nm light at a fluence rate of 4 mW/cm2 for 30 minutes, resulting in a fluence of 7.2 J/cm2. In planktonic cultures, MB-PDT was effective against Escherichia coli, Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA) (4- to 7-fold log CFU reduction). For Klebsiella pneumoniae, increased fluence was required to achieve comparable efficacy. When bacteria were grown as biofilms on silicone, MB-PDT efficacy was reduced (1- to 2-fold CFU reduction). A 3D silicone model was generated based on pelvic abscess CT images, and MRSA was grown in this model for six days. Crystal violet staining showed abundant growth on the silicone, without penetration into the model. These results motivate exploration of both light and drug dose ranging for biofilm samples. Future experiments will additionally focus on MB-PDT of bacteria grown on 3D silicone surfaces.

First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy by in vivo diffuse reflectance spectroscopy.

Significance: Efficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects. Aim: The objective was to extract optical properties and photosensitizer concentration from spatially-resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a Phase 1 clinical trial. Approach: Diffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties. Results: Pre-MB abscess wall absorption coefficients at 665 nm were 0.15±0.1 cm -1 (0.03-0.36 cm -1 ) and 10.74±15.81 cm -1 (0.08-49.3 cm -1 ) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm -1 (4.8-13.2 cm -1 ) and 5.6±2.26 cm -1 (1.6-9.9 cm -1 ) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83±35.78% (5.6-100%) pre-MB and 36.29±25.1% (0.0001-76.4%) post-MB. Determined MB concentrations were 71.83±108.22 µM (0-311 µM). Conclusions: We observed substantial inter-subject variation in both native wall optical properties and methylene blue uptake. This underscores the importance of making these measurements for patient-specific treatment planning.