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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 μ's at 665 nm (μ's,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 μ's,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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Increasing diversity is essential not only for equal healthcare among all individuals but also for equal socio-economic potential for all genders and ethnicities. With changing demographics over the years, we tried to assess the impact of university programs for the promotion of equality in ethnic representation in the medical community. The US population, based on the data taken from the US Census Bureau, was compared to the Faculty Administrative Management Online User System (FAMOUS) data to analyze the representation of the medical community to the general US population. Females have reached near parity in their representation within the medical community faculty. Underrepresented in medicine individuals have not come far enough to reach parity in their representation within the medical community. As compared to the general US population, while Asians are overrepresented, Black and Hispanic proportions in the medical community are still underrepresented. [ABSTRACT FROM AUTHOR]

We propose photodynamic therapy (PDT) as an adjunct for recurrent or difficult to treat abscesses, or where placement of a drainage catheter is undesirable. I ClinicalTrials.gov Identifier i NCT02240498 Interventional radiological draining of abscesses has become the standard of care treatment for abscesses unresponsive to conservative management. 1Pre-procedure CT showing tubo-ovarian abscess (horizontal arrow) Therefore, the abscess was percutaneously drained and PDT was performed as part of an ongoing Phase 1 clinical trial. [Extracted from the article]

Purpose: The aim was to determine the impact of steroid dose on effectiveness of CT-guided pudendal nerve blocks. Secondary aim was to assess predictors for response. Materials and methods: A retrospective cohort study was performed. Two-hundred-and-seventeen patients with pudendal neuralgia were identified. Of these, 189 patients had data on response and 511 pudendal nerve blocks were analyzed. Demographics, social history, initial pain data, treatment data including steroid dosing, and follow-up data were collected. Non-responders to treatment were compared to responders. Results: The majority of patients were female (92.1%) and most common areas of pain involved the vulva/labia/ perineum/vagina (scrotum) (44.2%). Treatment response rates increased with number of blocks with maximum response rate of 92.2% after fourth injection. Responders underwent more blocks within the first year (3.1 ± 1.5 vs 2.6 ± 1.6, p = 0.026). Steroid dose did not have a significant effect on response rate nor did site of injection. Non-responders were more commonly on disability due to pain (p = 0.043). History of childhood/adolescent sexual abuse was more common in non-responders (p=0.046) and was a significant predictor of response (OR = 0.27 [0.08–0.94 95% confidence interval], p = 0.04). Conclusion: Steroid dose does not appear to have an impact on the short-term response rates to CT-guided pudendal nerve blocks in patients with clinically diagnosed pudendal neuralgia and our data may further support the discontinuation of steroids from CT block protocols. Current long-term disability leave status was a predictor of poor response along with history of childhood/adolescent sexual abuse. Adverse childhood events are easily assessed and may represent a clinical predictor of lack of response in this patient population. Clinical relevance: Approaches to managing pudendal neuralgia are varied. Steroid dose may not impact response to pudendal nerve blocks. Current disability status and history of childhood/adolescent sexual abuse may be clinical predictors of poor response to treatment. [ABSTRACT FROM AUTHOR]

Abstract: Low back pain is the most common pain condition and cause for disability in older adults. Older adults suffering from low back pain are more disabled than their healthy peers, are more predisposed to frailty, and tend to be undertreated. The cause of increased prevalence and severity of this chronic pain condition in older adults is unknown. Here, we draw on accumulating data demonstrating a critical role for brain limbic and sensory circuitries in the emergence and experience of chronic low back pain (CLBP) and the availability of resting-state brain activity data collected at different sites to study how brain activity patterns predictive of CLBP differ between age groups. We apply a data-driven multivariate searchlight analysis to amplitude of low-frequency fluctuation brain maps to classify patients with CLBP with >70% accuracy. We observe that the brain activity pattern including the paracingulate gyrus, insula/secondary somatosensory area, inferior frontal, temporal, and fusiform gyrus predicted CLBP. When separated by age groups, brain patterns predictive of older patients with CLBP showed extensive involvement of limbic brain areas including the ventromedial prefrontal cortex, the nucleus accumbens, and hippocampus, whereas only anterior insula paracingulate and fusiform gyrus predicted CLBP in the younger patients. In addition, we validated the relationships between back pain intensity ratings and CLBP brain activity patterns in an independent data set not included in our initial patterns' identification. Our results are the first to directly address how aging affects the neural signature of CLBP and point to an increased role of limbic brain areas in older patients with CLBP. [ABSTRACT FROM AUTHOR]

Quantitative fluorescence spectroscopy requires corresponding reflectance measurements to correct tissue absorption and scattering. However, it is unclear whether fluorescence adds value beyond the diffuse reflectance measurements necessary for correction. The goal of this study was to compare the accuracy of fluorescence and diffuse reflectance spectroscopy in recovering the concentration of a high-extinction fluorophore, methylene blue (MB), using a compact fibre-optic probe. Fluorescence and diffuse reflectance measurements of tissue simulating phantoms were made using a fibre-optic probe with source-detector separations of 288–1300 µm. The average error in recovered fluorophore concentration was 20.4% for fluorescence and 15.0% for reflectance, though this difference was not significant (p = 0.77). Both methods returned concentrations that were similar to known MB concentrations (p ≥ 0.79 in both cases). Fluorescence quantification of the concentration of a high-extinction fluorophore did not significantly improve accuracy relative to diffuse reflectance. Investigators should consider whether fluorescence measurements are necessary for a given application. Trial registration ClinicalTrials.gov identifier: NCT02240498. [ABSTRACT FROM AUTHOR]

Background: Perceived fatigue is among the most common complaints in older adults and is substantially influenced by diminished resources or impaired structure of widespread cortical and subcortical regions. Alzheimer's disease and its preclinical stage-mild cognitive impairment (MCI)-are considered a brain network disease. It is unknown, however, whether those with MCI will therefore perceive worse fatigue, and whether an impaired global brain network will worsen their experience of fatigue.Methods: In this pilot case-control study of age-, sex-, and education-matched MCI and their cognitively healthy counterparts (HCs), perceived fatigue was measured using Multidimensional Fatigue Inventory, and diffusion tensor imaging tractography data were analyzed using graph theory methods to explore small-worldness properties: segregation and integration.Results: Perceived fatigue was more severe in MCI than HCs. Despite a trend for greater network alterations in MCI, there were no significant group differences in integration or segregation. Greater perceived fatigue was related to higher segregation across groups; more perceived fatigue was related to higher segregation and lower integration in MCI but not HCs.Conclusion: Findings of this study support the notion that altered whole-brain small-worldness properties in brain aging or neurodegeneration may underpin perceived fatigue. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is a vital component of high-quality Obstetric care. In rural and under-resourced communities, the scarcity of ultrasound imaging results in a considerable gap in the healthcare of pregnant mothers. To increase access to ultrasound in these communities, we developed a new automated diagnostic framework operated without an experienced sonographer or interpreting provider for assessment of fetal biometric measurements, fetal presentation, and placental position. This approach involves the use of a standardized volume sweep imaging (VSI) protocol based solely on external body landmarks to obtain imaging without an experienced sonographer and application of a deep learning algorithm (U-Net) for diagnostic assessment without a radiologist. Obstetric VSI ultrasound examinations were performed in Peru by an ultrasound operator with no previous ultrasound experience who underwent 8 hours of training on a standard protocol. The U-Net was trained to automatically segment the fetal head and placental location from the VSI ultrasound acquisitions to subsequently evaluate fetal biometry, fetal presentation, and placental position. In comparison to diagnostic interpretation of VSI acquisitions by a specialist, the U-Net model showed 100% agreement for fetal presentation (Cohen's κ 1 (p<0.0001)) and 76.7% agreement for placental location (Cohen's κ 0.59 (p<0.0001)). This corresponded to 100% sensitivity and specificity for fetal presentation and 87.5% sensitivity and 85.7% specificity for anterior placental location. The method also achieved a low relative error of 5.6% for biparietal diameter and 7.9% for head circumference. Biometry measurements corresponded to estimated gestational age within 2 weeks of those assigned by standard of care examination with up to 89% accuracy. This system could be deployed in rural and underserved areas to provide vital information about a pregnancy without a trained sonographer or interpreting provider. The resulting increased access to ultrasound imaging and diagnosis could improve disparities in healthcare delivery in under-resourced areas. [ABSTRACT FROM AUTHOR]

Background: Hepatic and biliary diseases are prevalent worldwide, but the majority of people lack access to diagnostic medical imaging for their assessment. The liver and gallbladder are readily amenable to sonographic examination, and ultrasound is a portable, cost-effective imaging modality suitable for use in rural and underserved areas. However, the deployment of ultrasound in these settings is limited by the lack of experienced sonographers to perform the exam. In this study, we tested an asynchronous telediagnostic system for right upper quadrant abdominal ultrasound examination operated by individuals without prior ultrasound experience to facilitate deployment of ultrasound to rural and underserved areas. Methods: The teleultrasound system utilized in this study employs volume sweep imaging and a telemedicine app installed on a tablet which connects to an ultrasound machine. Volume sweep imaging is an ultrasound technique in which an individual scans the target region utilizing preset ultrasound sweeps demarcated by easily recognized external body landmarks. The sweeps are saved as video clips for later interpretation by an experienced radiologist. Teleultrasound scans from a Peruvian clinic obtained by individuals without prior ultrasound experience were sent to the United States for remote interpretation and quality assessment. Standard of care comparison was made to a same-day ultrasound examination performed by a radiologist. Results: Individuals without prior ultrasound experience scanned 144 subjects. Image quality was rated "poor" on 36.8% of exams, "acceptable" on 38.9% of exams, and "excellent" on 24.3% of exams. Among telemedicine exams of "acceptable" or "excellent" image quality (n = 91), greater than 80% of the liver and gallbladder were visualized in the majority of cases. In this group, there was 95% agreement between standard of care and teleultrasound on whether an exam was normal or abnormal, with a Cohen's kappa of 0.84 (95% CI 0.7–0.98, p <0.0001). Finally, among these teleultrasound exams of "acceptable" or "excellent" image quality, the sensitivity for cholelithiasis was 93% (95% CI 68.1%-99.8%), and the specificity was 97% (95% CI 89.5%-99.6%). Conclusion: This asynchronous telediagnostic system allows individuals without prior ultrasound experience to effectively scan the liver, gallbladder, and right kidney with a high degree of agreement with standard of care ultrasound. This system can be deployed to improve access to diagnostic imaging in low-resource areas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Deep tissue abscesses represent a significant source of morbidity and hospital stay, with standard of care drainage failing in many cases. We investigated photodynamic therapy (PDT) as an adjunct to standard of care, to reduce or eliminate bacterial burden. A Phase 1 clinical trial was performed to evaluate safety and feasibility of methylene blue (MB) PDT at the time of abscess drainage. Immediately following drainage, MB-PDT was performed. Diffuse reflectance spectroscopy was performed to evaluate abscess wall optical properties. No study-related adverse events were noted, and no side effects were observed. PDT was well tolerated by all subjects, and infused MB was recovered in all cases. Optical property measurements showed variability in hemoglobin concentration and oxygenation, as well as MB uptake, between subjects. MB-PDT at the time of percutaneous abscess drainage was safe and feasible, and optical property measurements showed wide variance between subjects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Deep tissue abscesses remain a serious cause of morbidity, mortality, and hospital stay despite development of percutaneous drainage and increasing use of perioperative antibiotics. The goal of this study was to examine the feasibility of methylene blue (MB) mediated photodynamic therapy (PDT) for treatment of infected abscesses with intracavity MB delivery, using computed tomography (CT) imaging data from a representative abscess patient population and Monte Carlo simulation of light delivery. Methods: This retrospective study included all adult subjects that received percutaneous abscess drainage between 1 January 2014 and 31 December 2014 at our institution whose abscess was confirmed by abdominal CT imaging less than 1 week preprocedure (n = 358). Of these, 40 subjects were further analyzed with Monte Carlo simulation. Abscess volumes were segmented from CT images, and imported into the Monte Carlo simulation space. Monte Carlo simulations were performed with a single fiber placement for each abscess, with the optical power at which a fluence rate of either 4 or 20 mW/cm2 was achieved for 95% of the abscess wall recorded. Subjects for which a fluence rate of 4 mW/cm2 was attainable in 95% of the abscess wall with a maximum input optical power of 2000 mW were considered eligible for MB‐PDT. Results: 42.5% of subjects would have been eligible for MB‐PDT, with 17.5% attaining the higher threshold of 20 mW/cm2 in 95% of the abscess wall, given a 1% Intralipid concentration within the abscess cavity and the assumed abscess wall optical properties. The mean optical power necessary was 680 ± 580 mW for the 4 mW/cm2 threshold, and 1100 ± 600 mW for the 20 mW/cm2 threshold. Abscess surface area and threshold optical power were correlated (Spearman ρ = 0.73, P = 0.001), with larger abscesses requiring higher optical power. Of the subjects who were not eligible for MB‐PDT, abscess volumes (150 ± 120 vs 62 ± 41 cm3, P = 0.0049) and surface areas (320 ± 200 vs 140 ± 70 cm2, P = 0.0015) tended to be larger than for those who were eligible. There were no significant differences in eligibility, optical power required, or abscess volume or surface area based on abscess location. For all eligible subjects, at the optical power necessary to achieve 4 mW/cm2 in 95% of the abscess wall, 2.5 ± 3.7% (0%–13.2%) of the wall experienced a fluence rate greater than or equal to 400 mW/cm2. At the 20 mW/cm2 threshold, 8.8 ± 11.4% (0%–31.1%) of the wall surpassed this 400 mW/cm2 level. If subjects with greater than 5% of the wall exceeding 400 mW/cm2 are treated as ineligible, overall eligibility becomes 32.5% for the 4 mW/cm2 threshold and 10.0% for the 20 mW/cm2 threshold. Conclusions: Assuming that the subjects analyzed were representative of the overall patient population, over 150 patients that received percutaneous abscess drainage during the study period would have been eligible for MB‐PDT at the time of drainage, with smaller abscesses being more amenable for treatment. This technique could potentially reduce abscess recurrence, duration of drainage catheter placement, and reliance on systemic antibiotics. These results motivate a future Phase 2 clinical trial following successful completion of the ongoing safety study. [ABSTRACT FROM AUTHOR]

Background: Some individuals, called Supernormals (SN), maintain excellent memory in old age. While brain structural and functional integrity in SN seem to be aging-resistant, their amyloidosis and neural injury status has not been well studied.Objective: The goal of this study was to compare cortical amyloid deposition and glucose metabolism between SN and older adults with normal cognition (NC), amnestic mild cognitive impairment (MCI), and Alzheimer's disease (AD).Methods: Subjects from the ADNI database were included if they received T1-weighted MRI, amyloid PET, FDG-PET, and cognitive testing within a 6-month period, yielding 27 AD, 69 MCI, 172 NC, and 122 SN. PET standardized uptake value ratios (SUVrs) were calculated for the whole cortex and 68 regions of interest, with whole cerebellum serving as reference.Results: SN had lower whole cortex amyloid than MCI, and higher glucose metabolism than all others. Regional analysis revealed that amyloid burden and glucose metabolism in the right isthmus cingulate cortex differed in SN compared to others, while SN glucose metabolism also differed from others in several frontal and temporal regions.Conclusion: Preserved cortical glucose metabolism, and lower levels of amyloidosis and glucose hypometabolism in the right isthmus cingulate cortex, contributes to the Supernormal phenomenon. These findings may be informative for development of early screening biomarkers and therapeutic targets for modification of cognitive trajectories. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid- β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEɛ4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEɛ4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) ε4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEε4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2x2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid-β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEε4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEε4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics. [ABSTRACT FROM AUTHOR]

We demonstrate recovery of optical properties using arrays of interstitial cylindrical diffusing fibers as sources and detectors. A single 1-cm diffuser delivered laser illumination at 665 nm, while seven 1- and 2-cm diffusers at 1-cm grid spacing acted as detectors. Extraction of optical properties from these measurements was based upon a diffusion model of emission and detection distributions for these diffuser fibers, informed by previous measurements of heterogeneous axial detection. Verification of the technique was performed in 15 liquid tissue-simulating phantoms consisting of deionized water, India ink as absorber, and Intralipid 20% as scatterer. For the range of optical properties tested, mean errors were 4.4% for effective attenuation coefficient, 12.6% for absorption coefficient, and 7.6% for reduced scattering coefficient. Error in recovery tended to increase with decreasing transport albedo. For therapeutic techniques involving the delivery of light to locations deep within the body, such as interstitial photodynamic and photothermal therapies, the methods described here would allow the treatment diffuser fibers also to be used as sources and detectors for recovery of optical properties. This would eliminate the need for separately inserted fibers for spectroscopy, reducing clinical complexity and improving the accuracy of treatment planning. [ABSTRACT FROM AUTHOR]

Significance: Antimicrobial photodynamic therapy (PDT) effectively kills bacterial strains found in deep tissue abscess cavities. PDT response hinges on multiple factors, including light dose, which depends on patient optical properties. Aim: Computed tomography images for 60 abscess drainage subjects were segmented and used for Monte Carlo (MC) simulation. We evaluated effects of optical properties and abscess morphology on PDT eligibility and generated treatment plans. Approach: A range of abscess wall absorptions (μa , wall) and intra-cavity Intralipid concentrations were simulated. At each combination, the threshold optical power and optimal Intralipid concentration were found for a fluence rate target, with subjects being eligible for PDT if the target was attainable with <2000 mW of source light. Further simulations were performed with absorption within the cavity (μa , cavity). Results: Patient-specific treatment planning substantially increased the number of subjects expected to achieve an efficacious light dose for antimicrobial PDT, especially with Intralipid modification. The threshold optical power and optimal Intralipid concentration increased with increasing μa , wall (p < 0.001). PDT eligibility improved with patient-specific treatment planning (p < 0.0001). With μa , wall = 0.2 cm − 1, eligibility increased from 42% to 92%. Increasing μa , cavity reduced PDT eligibility (p < 0.0001); modifying the delivered optical power had the greatest impact in this case. Conclusions: MC-based treatment planning greatly increases eligibility for PDT of abscess cavities. [ABSTRACT FROM AUTHOR]

Purpose: For interstitial photodynamic therapy (iPDT) of bulky tumors, careful treatment planning is required in order to ensure that a therapeutic dose is delivered to the tumor, while minimizing damage to surrounding normal tissue. In clinical contexts, iPDT has typically been performed with either flat cleaved or cylindrical diffusing optical fibers as light sources. Here, the authors directly compare these two source geometries in terms of the number of fibers and duration of treatment required to deliver a prescribed light dose to a tumor volume. Methods: Treatment planning software for iPDT was developed based on graphics processing unit enhanced Monte Carlo simulations. This software was used to optimize the number of fibers, total energy delivered by each fiber, and the position of individual fibers in order to deliver a target light dose (D90) to 90% of the tumor volume. Treatment plans were developed using both flat cleaved and cylindrical diffusing fibers, based on tissue volumes derived from CT data from a head and neck cancer patient. Plans were created for four cases: fixed energy per fiber, fixed number of fibers, and in cases where both or neither of these factors were fixed. Results: When the number of source fibers was fixed at eight, treatment plans based on flat cleaved fibers required each to deliver 7180-8080 J in order to deposit 90 J/cm2 in 90% of the tumor volume. For diffusers, each fiber was required to deliver 2270-2350 J (333-1178 J/cm) in order to achieve this same result. For the case of fibers delivering a fixed 900 J, 13 diffusers or 19 flat cleaved fibers at a spacing of 1 cm were required to deliver the desired dose. With energy per fiber fixed at 2400 J and the number of fibers fixed at eight, diffuser fibers delivered the desired dose to 93% of the tumor volume, while flat cleaved fibers delivered this dose to 79%. With both energy and number of fibers allowed to vary, six diffusers delivering 3485-3600 J were required, compared to ten flat cleaved fibers delivering 2780-3600 J. Conclusions: For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume. [ABSTRACT FROM AUTHOR]

We examined effects of fluence rate on the photobleaching of the photosensitizer Pc 4 during photodynamic therapy (PDT) and the relationship between photobleaching and tumor response to PDT. BALB/c mice with intradermal EMT6 tumors were given 0.03 mg kg−1 Pc 4 by intratumor injection and irradiated at 667 nm with an irradiance of 50 or 150 mW cm−2 to a fluence of 100 J cm−2. While no cures were attained, significant tumor growth delay was demonstrated at both irradiances compared with drug-only controls. There was no significant difference in tumor responses to these two irradiances ( P = 0.857). Fluorescence spectroscopy was used to monitor the bleaching of Pc 4 during irradiation, with more rapid bleaching with respect to fluence shown at the higher irradiance. No significant correlation was found between fluorescence photobleaching and tumor regrowth for the data interpreted as a whole. Within each treatment group, weak associations between photobleaching and outcome were observed. In the 50 mW cm−2 group, enhanced photobleaching was associated with prolonged growth delay ( P = 0.188), while at 150 mW cm−2 this trend was reversed ( P = 0.308). Thus, it appears that Pc 4 photobleaching is not a strong predictor of individual tumor response to Pc 4-PDT under these treatment conditions. [ABSTRACT FROM AUTHOR]

The axial emission and detection profiles of 1- and 2-cm cylindrical diffusing fibers based on concentration gradients of scatterers were measured. Based on these measurements, we describe a method for determination of the scatterer concentration gradient within the diffusers. Using a Monte Carlo model incorporating these concentrations, detection was simulated and found to agree with measurements. The measured and simulated detection profiles for these diffusers were found to be drastically different from those previously measured in an alternative diffuser design incorporating an end reflector. When using cylindrical diffusers as detection fibers, it is, therefore, important to understand the design of the fiber and characterize the detection behavior. [ABSTRACT FROM AUTHOR]

Fluorescent proteins can generate reactive oxygen species (ROS) upon absorption of photons via type I and II photosensitization mechanisms. The red fluorescent proteins KillerRed and SuperNova are phototoxic proteins engineered to generate ROS and are used in a variety of biological applications. However, their relative quantum yields and rates of ROS production are unclear, which has limited the interpretation of their effects when used in biological systems. We cloned and purified KillerRed, SuperNova, and mCherry - a related red fluorescent protein not typically considered a photosensitizer - and measured the superoxide (O 2 •-) and singlet oxygen (1O 2) quantum yields with irradiation at 561 nm. The formation of the O 2 •--specific product 2-hydroxyethidium (2-OHE+) was quantified via HPLC separation with fluorescence detection. Relative to a reference photosensitizer, Rose Bengal, the O 2 •- quantum yield (ΦO 2 •-) of SuperNova was determined to be 1.5 × 10-3, KillerRed was 0.97 × 10-3, and mCherry 1.2 × 10-3. At an excitation fluence of 916.5 J/cm2 and matched absorption at 561 nm, SuperNova, KillerRed and mCherry made 3.81, 2.38 and 1.65 μM O 2 •-/min, respectively. Using the probe Singlet Oxygen Sensor Green (SOSG), we ascertained the 1O 2 quantum yield (Φ1O 2) for SuperNova to be 22.0 × 10-3, KillerRed 7.6 × 10-3, and mCherry 5.7 × 10-3. These photosensitization characteristics of SuperNova, KillerRed and mCherry improve our understanding of fluorescent proteins and are pertinent for refining their use as tools to advance our knowledge of redox biology. Image 1 • We report O 2 •- and 1O 2 quantum yields for KillerRed, SuperNova and mCherry. • O 2 •- generation was measured using HPLC separation of 2-OHE+ and 1O 2 with SOSG. • Supernova's O 2 •- and 1O 2 yields are larger than those of KillerRed and mCherry. • O 2 •- quantum yield of mCherry is comparable to those of KillerRed and SuperNova. [ABSTRACT FROM AUTHOR]