Immune Modulation Permits Tolerance and Engraftment in a Murine Model of Late-Gestation Transplantation.

In utero hematopoietic cell transplantation (IUHCT) is an experimental non-myeloablative therapy with potential application to hematologic disorders including Sickle cell disease. Its clinical utility has been limited due to the early acquisition of T cell immunity beginning at approximately 14 weeks gestation, posing significant technical challenges and excluding from treatment fetuses evaluated after the first trimester. Using murine neonatal transplantation at 20 days post-coitum (DPC) as a model for late-gestation transplantation (LGT) in humans, we investigated whether immune modulation with anti-CD3 monoclonal antibody (mAb) could achieve donor-specific tolerance and sustained allogeneic engraftment comparable to the early-gestation fetal recipient at 14 DPC. In allogeneic wild-type strain combinations, administration of anti-CD3 mAb with transplantation resulted in transient T cell depletion followed by central tolerance induction confirmed by donor-specific clonal deletion and skin graft tolerance. Normal immune responses to third-party major histocompatibility complex and viral pathogens were preserved, and graft-versus-host disease did not occur. We further demonstrate successful application of this approach to the Townes mouse model of Sickle cell disease. These findings confirm the developing fetal T cell response as a barrier to LGT and support transient T cell depletion as a safe and effective immunomodulatory strategy by which to overcome it.

Orthotospovirus iridimaculaflavi (iris yellow spot virus): An emerging threat to onion cultivation and its transmission by Thrips tabaci in India.

The yellow spot disease caused by the virus species Orthotospovirus iridimaculaflavi (Iris yellow spot virus-IYSV), belonging to the genus Orthotospovirus, the family Tospoviridae, order Bunyavirales and transmitted by Thrips tabaci Lindeman. At present, emerging as a major threat in onion (Allium cepa) in Tamil Nadu, India. The yellow spot disease incidence was found to be 53-73 % in six districts out of eight major onion-growing districts surveyed in Tamil Nadu during 2021-2023. Among the onion cultivars surveyed, the cultivar CO 5 was the most susceptible to IYSV. The population of thrips was nearly 5-9/plant during vegetative and flowering stages. The thrips infestation was 34-60 %. The tospovirus involved was confirmed as IYSV through DAS-ELISA, followed by molecular confirmation through RT-PCR using the nucleocapsid (N) gene. The predominant thrips species present in onion crops throughout the growing seasons was confirmed as Thrips tabaci based on the nucleotide sequence of the MtCOI gene. The mechanical inoculation of IYSV in different hosts viz., Vigna unguiculata, Gomphrena globosa, Chenopodium amaranticolor, Chenopodium quinoa and Nicotiana benthamiana resulted in chlorotic and necrotic lesion symptoms. The electron microscopic studies with partially purified sap from onion lesions revealed the presence of spherical to pleomorphic particles measuring 100-230 nm diameter. The transmission of IYSV was successful with viruliferous adult Thrips tabaci in cowpea (Cv. CO7), which matured from 1st instar larva fed on infected cowpea leaves (24 h AAP). Small brown necrotic symptoms were produced on inoculated plants after an interval of four weeks. The settling preference of non-viruliferous and viruliferous T. tabaci towards healthy and infected onion leaves resulted in the increased preference of non-viruliferous thrips towards infected (onion-61.33 % and viruliferous thrips towards healthy onion leaves (75.33 %). The study isolates shared 99-100 % identity at a nucleotide and amino acid level with Indian isolates of IYSV in the N gene. The multiple alignment of the amino acid sequence of the N gene of IYSV isolates collected from different locations and IYSV isolates from the database revealed amino acid substitution in the isolate ITPR4. All the IYSV isolates from India exhibited characteristic amino acid substitution of serine at the 6th position in the place of threonine in the isolates from Australia, Japan and USA. The phylogenetic analysis revealed the monophyletic origin of the IYSV isolates in India.

Ultrasound and Photoacoustic Imaging for the Guidance of Laser Ablation Procedures.

The accuracy and efficacy of laser ablation procedures depend on the accurate placement of the laser applicator within the diseased tissue, monitoring the real-time temperature during the ablation procedure, and mapping the extent of the ablated region. Ultrasound (US) imaging has been widely used to guide ablation procedures. While US imaging offers significant advantages for guiding ablation procedures, its limitations include low imaging contrast, angular dependency, and limited ability to monitor the temperature. Photoacoustic (PA) imaging is a relatively new imaging modality that inherits the advantages of US imaging and offers enhanced capabilities for laser-guided ablations, such as accurate, angle-independent tracking of ablation catheters, the potential for quantitative thermometry, and monitoring thermal lesion formation. This work provides an overview of ultrasound-guided procedures and how different US-related artifacts limit their utility, followed by introducing PA as complementary to US as a solution to address the existing limitations and improve ablation outcomes. Furthermore, we highlight the integration of PA-driven features into existing US-guided laser ablation systems, along with their limitations and future outlooks. Integrated US/PA-guided laser ablation procedures can lead to safer and more precise treatment outcomes.

Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells.

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

RNASeq Analysis for Accurate Identification of Fusion Partners in Tumor Specific Translocations Detected by Standard FISH Probes in Hematologic Malignancies.

Background: Fluorescence labeled DNA probes and in situ hybridization methods had shorter turn round time for results revolutionized their clinical application. Signals obtained from these probes are highly specific, yet they can produce fusion signals not necessarily representing fusion of actual genes due to other genes included in the probe design. In this study we evaluated discordance between cytogenetic, FISH and RNAseq results in 3 different patients with hematologic malignancies and illustrated the need to perform next generation sequencing (NGS) or RNASeq to accurately interpret FISH results. Methods: Bone marrow or peripheral blood karyotypes and FISH were performed to detect recurring translocations associated with hematologic malignancies in clinical samples routinely referred to our clinical cytogenetics laboratory. When required, NGS was performed on DNA and RNA libraries to detect somatic alterations and gene fusions in some of these specimens. Discordance in results between these methods is further evaluated. Results: For a patient with plasma cell leukemia standard FGFR3 / IGH dual fusion FISH assay detected fusion that was interpreted as FGFR3-positive leukemia, whereas NGS/RNASeq detected NSD2::IGH. For a pediatric acute lymphoblastic leukemia patient, a genetic diagnosis of PDGFRB-positive ALL was rendered because the PDGFRB break-apart probe detected clonal rearrangement, whereas NGS detected MEF2D::CSF1R. A MYC-positive B-prolymphocytic leukemia was rendered for another patient with a cytogenetically identified t(8;14) and MYC::IGH by FISH, whereas NGS detected a novel PVT1::RCOR1 not previously reported. Conclusions: These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.

Clinicopathologic features of relapsed CD19(-) B-ALL in CD19-targeted immunotherapy: Biological insights into relapse and LILRB1 as a novel B-cell marker for CD19(-) B lymphoblasts.

INTRODUCTION: The mechanism of relapsed CD19(-) B-ALL after anti-CD19 immunotherapy (Kymriah [CART-19] and blinatumomab) is under active investigation. Our study aims to assess LILRB1 as a novel B-cell marker for detecting CD19(-) B-lymphoblasts and to analyze the clinicopathologic/genetic features of such disease to provide biological insight into relapse. METHODS: Six patients (3 males/3 females, median age of 14 years) with relapsed CD19(-) B-ALL were analyzed for cytogenetic/genetic profile and immunophenotype. RESULTS: CD19(-) B-ALL emerged after an interval of 5.8 months following anti-CD19 therapy. Five of six patients had B-cell aplasia, indicative of a persistent effect of CART or blinatumomab at relapse. Importantly, LILRB1 was variably expressed on CD19(-) and CD19(+) B lymphoblasts, strong on CD34(+) lymphoblasts and dim/partial on CD34(-) lymphoblasts. Three of six patients with paired B-ALL samples (pre- and post-anti-CD19 therapy) carried complex and different cytogenetic abnormalities, either as completely different or sharing a subset of cytogenetic abnormalities. CONCLUSION: LILRB1 can be used as a novel B-cell marker to identify CD19(-) B lymphoblasts. The emergence of CD19(-) B-ALL appears to be associated with complex cytogenetic evolutions. The mechanism of CD19(-) B-ALL relapse under anti-CD19 immune pressure remains to be explored by comprehensive molecular studies.

LILRB3 Supports Immunosuppressive Activity of Myeloid Cells and Tumor Development.

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.

Mediport use as an acceptable standard for CAR T cell infusion.

Introduction: Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions. Methods: In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017. Results: Across 34 sites, all reported tunneled central venous catheters, including Broviac® and Hickman® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration. Discussion/Conclusion: Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.

Niche preclinical and clinical applications of photoacoustic imaging with endogenous contrast.

In the past decade, photoacoustic (PA) imaging has attracted a great deal of popularity as an emergent diagnostic technology owing to its successful demonstration in both preclinical and clinical arenas by various academic and industrial research groups. Such steady growth of PA imaging can mainly be attributed to its salient features, including being non-ionizing, cost-effective, easily deployable, and having sufficient axial, lateral, and temporal resolutions for resolving various tissue characteristics and assessing the therapeutic efficacy. In addition, PA imaging can easily be integrated with the ultrasound imaging systems, the combination of which confers the ability to co-register and cross-reference various features in the structural, functional, and molecular imaging regimes. PA imaging relies on either an endogenous source of contrast (e.g., hemoglobin) or those of an exogenous nature such as nano-sized tunable optical absorbers or dyes that may boost imaging contrast beyond that provided by the endogenous sources. In this review, we discuss the applications of PA imaging with endogenous contrast as they pertain to clinically relevant niches, including tissue characterization, cancer diagnostics/therapies (termed as theranostics), cardiovascular applications, and surgical applications. We believe that PA imaging's role as a facile indicator of several disease-relevant states will continue to expand and evolve as it is adopted by an increasing number of research laboratories and clinics worldwide.

Ascorbic acid attenuates cadmium-induced myocardial hypertrophy and cardiomyocyte injury through Nrf2 signaling pathways comparable to resveratrol.

Chronic cadmium (Cd) exposure severely affects the structural integrity of the heart, leading to cardiovascular disease. This study investigates the protective role of ascorbic acid (AA) and resveratrol (Res) in cellular defense against Cd-induced cardiomyocyte damage and myocardial hypertrophy in H9c2 cardiomyocytes. Experimental results showed that AA and Res treatment significantly increased cell viability, reduced ROS production, attenuated lipid peroxidation, and increased antioxidant enzyme activity in Cd-induced H9c2 cells. AA and Res decreased the mitochondrial membrane permeability and protected the cells from Cd induced cardiomyocyte damage. This also suppressed the pathological hypertrophic response triggered by Cd, which increased the cell size of cardiomyocytes. Gene expression studies revealed that cells treated with AA and Res decreased the expression of hypertrophic genes ANP (two-fold), BNP (one-fold) and ß- MHC (two-fold) compared to Cd exposed cells. AA and Res promoted the nuclear translocation of Nrf2 and increased the expression of antioxidant genes (HO-1, NQO1, SOD and CAT) during Cd mediated myocardial hypertrophy. This study proves that AA and Res play a significant role in improving Nrf2 signaling, thereby reversing stress-induced injury, and facilitating the regression of myocardial hypertrophy.

Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells.

Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplantation, is critical and warrants further investigation on prospective clinical trials.

Integrated Ultrasound and Photoacoustic-Guided Laser Ablation Theranostic Endoscopic System.

Advancements in ablation techniques have paved the way towards the development of safer and more effective clinical procedures for treating various maladies such as atrial fibrillation (AF). AF is characterized by rapid, chaotic atrial activation and is commonly treated using radiofrequency applicators or laser ablation catheters. However, the lack of thermal lesion formation and temperature monitoring capabilities in these devices prevents them from measuring the treatment outcome directly. In addition, poor differentiation between healthy and ablated tissues leads to incomplete ablation, which reduces safety and causes complications in patients. Hence, a novel photoacoustic (PA)-guided laser ablation theranostic device was developed around a traditional phased-array endoscope. The proposed technology provides lesion formation, tissue distinguishing, and temperature monitoring capabilities. Our results have validated the lesion monitoring capability of the proposed technology through PA correlation maps. The tissue distinguishing capability of the theranostic device was verified by the measurable differences in the PA signal between pre-and post-ablated mice myocardial tissue. The increase in the PA signal with temperature variations caused by the ablation laser confirmed the ability of the proposed device to provide temperature feedback.

Ex Vivo Evaluation of a Minimally Invasive Approach for Cochlear Implant Surgery.

OBJECTIVES: Drilling a minimally invasive access to the inner ear is a demanding task in which a computer-assisted surgical system can support the surgeon. Herein, we describe the design of a new micro-stereotactic targeting system dedicated to cochlear implant (CI) surgery and its experimental evaluation in an ex vivo study. METHODS: The proposed system consists of a reusable, bone-anchored reference frame, and a patient-specific drilling jig on top of it. Individualization of the jig is simplified to a single counterbored hole drilled out of a blank. For accurate counterboring, the setup includes a manufacturing device for individual positioning of the blank. The system was tested in a preclinical setting using twelve human cadaver donors. Cone beam computed tomograph (CBCT) scans were obtained and a drilling trajectory was planned pointing towards the basal part of the cochlea. The surgical drill was moved forward manually and slowly while the jig constrained the drill along the predetermined path. RESULTS: Drilling could be performed with preservation of facial nerve in all specimens. The mean error caused by the system at the target point in front of the cochlea was 0.30 mm ± 0.11 mm including an inaccuracy of 0.09 mm ± 0.03 mm for counterboring the guiding aperture into the jig. CONCLUSION: Feasibility of the proposed system to perform a minimally invasive posterior tympanotomy approach was shown successfully in all specimens. SIGNIFICANCE: First evaluation of the new system in a comprehensive ex vivo study demonstrating sufficient accuracy and the feasibility of the whole concept.

Minimally Invasive Cochlear Implantation: First-in-Man of Patient-Specific Positioning Jigs.

A minimally-invasive surgical (MIS) approach to cochlear implantation, if safe, practical, simple in surgical handling, and also affordable has the potential to replace the conventional surgical approaches. Our MIS approach uses patient-specific drilling templates (positioning jigs). While the most popular MIS approaches use robots, the robotic aspect is literally put aside, because our high-precision parallel kinematics is only used to individualize a positioning jig. This jig can then be mounted onto a bone-anchored mini-stereotactic frame at the patient's skull and used to create a drill-hole through the temporal bone to the patient's cochlea. We present the first clinical experience where we use sham drill bits of different diameters instead of drilling into the bone in order to demonstrate the feasibility and accuracy.

Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL.

PURPOSE: CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS: We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS: Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naïve patients. Among patients evaluable for CD19-CAR response (n = 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P < .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P < .0001) or blinatumomab-naïve patients (72.6%; 95% CI, 67.5 to 77; P < .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P = .06) and associated with lower EFS and RFS. CONCLUSION: With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR.

Evaluation of albumin use in a community hospital setting: A retrospective study looking at appropriate use and prescribing patterns.

PURPOSE: Albumin has been shown to be safe and effective in clinical practice for a wide variety of indications. The purpose of this medication use evaluation is to quantify the use of albumin in the community hospital setting based on indication and prescribing department. METHODS: This study is a retrospective, single-center, chart review over a 6-month period of 186 patients aged 18 and older who were treated with IV human albumin 5% or 25% at a single 202-bed community hospital setting from February 1, 2020, to August 1, 2020. A chart review was completed for each patient and the data collected included date of albumin administration, the ordering provider, the specialty of the provider, the indication for albumin as stated in the order, patient notes, crystalloid therapy use prior to albumin, albumin strength, the presence of acute or chronic renal, hepatic or respiratory disorders, and lab values denoting renal and hepatic function. Appropriate albumin use was determined utilizing criteria which included FDA labeled indications, the Surviving Sepsis Campaign, and existing literature. RESULTS: A total of 186 patients received albumin 5% or 25% IV solution at least once during the study period. The study population was 52.2% female, and the average age was 68 years. Of the patients selected for the study, 23 (11.6%) had chronic hepatic disease, and 37 (18.7%) had chronic renal disease. The top indications for which albumin was administered were sepsis or septic shock (25.3%), hypotension or hypovolemia (19.4%), intra-dialytic hypotension (13.4%), fluid support in surgery (10.8%), and nephrosis or nephropathy (10.8%). The departments with highest albumin use during this study period were critical care (41%), nephrology (28%), and surgery (17%). Overall, albumin was used for an appropriate indication in 126 out of 186 patients (67.7%). CONCLUSION: We found that albumin was most utilized for sepsis and septic shock, hypovolemia and hypotension, and intradialytic hypotension in our community hospital setting and it was most frequently ordered by critical care, nephrology, and surgical departments. Further research could determine if this trend is seen in other community hospital settings.

Functional aspects of the Eustachian tube by means of 3D-modeling.

The extent of dysfunction of the Eustachian tube (ET) is relevant in understanding the pathogenesis of secondary otological diseases such as acute or chronic otitis media. The underlying mechanism of ET dysfunction remains poorly understood except for an apparent genesis such as a nasopharyngeal tumor or cleft palate. To better describe the ET, its functional anatomy, and the biomechanical valve mechanism and subsequent development of diagnostic and interventional tools, a three-dimensional model based on thin-layer histology was created from an ET in this study. Blackface sheep was chosen as a donor. The 3-D model was generated by the coherent alignment of the sections. It was then compared with the cone-beam computed tomography dataset of the complete embedded specimen taken before slicing. The model shows the topographic relation of the individual components, such as the bone and cartilage, the muscles and connective tissue, as well as the lining epithelium with the lumen. It indicates a limited spiraling rotation of the cartilaginous tube over its length and relevant positional relationships of the tensor and levator veli palatine muscles.

Efficacy of High Temporal Frequency Photoacoustic Guidance of Laser Ablation Procedures.

Inaccurate placement of the ablation catheter and the inability to monitor the real-time temperature within the tissue of interest such as veins curbs the treatment efficacy of laser ablation procedures during thermal therapies. Our previous studies have validated the efficacy of photoacoustic (PA) imaging during endovenous laser ablation (EVLA) procedures. However, the PA-guided therapies suffer from low temporal resolution, due to the low pulse repetition rates of pulsed lasers, which could cause a problem during fast catheter motion and rapid temperature changes. Herein, to enhance the accuracy and sensitivity for tracking the ablation catheter tip and temperature monitoring, we proposed to develop a high frame rate (500 Hz), combined ultrasound (US), and PA-guided ablation system. The proposed PA-guided ablation system was evaluated in a set of ex vivo tissue studies. The developed system provides a 2 ms temporal resolution for tracking and monitoring the ablation catheter tip's location and temperature, which is 50 times higher temporal resolution compared to the previously proposed 10 Hz system. The proposed system also provided more accurate feedback about the temperature variations during rapid temperature increments of 10°C per 250 ms. The co-registered US and PA images have an imaging resolution of about 200 µm and a field of view of 45 × 40 mm2. Tracking the ablation catheter tip in an excised tissue layer shows higher accuracy during a relatively fast catheter motion (0.5-3 mm/s). The fast US/PA-guided ablation system will potentially enhance the outcome of ablation procedures by providing location and temperature feedback.