Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs.

Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68Ga]Ga-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs. NPI transplantation (3320-15,000 islet equivalents per kg body weight) led to a reduced need for exogenous insulin therapy and finally normalization of blood glucose levels in 3 out of 4 animals after 5 to 10 weeks. Longitudinal PET/CT measurements revealed a significant increase in standard uptake values in graft-bearing livers. Histologic analysis confirmed the presence of well-engrafted, mature islet clusters in the transplanted livers. Our study presents a novel large animal model for allogeneic intraportal ITx. A relatively small dose of NPIs was sufficient to normalize blood glucose levels in a clinically relevant diabetic pig model. [68Ga]Ga-DOTA-exendin-4 PET/CT proved to be efficacious for longitudinal monitoring of islet transplants. Thus, it could play a crucial role in optimizing ITx as a curative therapy for type 1 diabetes.

Molecular probes for monitoring pyroptosis: design, imaging and theranostic application.

Pyroptosis is a recently discovered process of programmed cell death that is linked with tumor progression and potential treatment strategies. Unlike other forms of programmed cell death, such as apoptosis or necrosis, pyroptosis is associated with pore-forming proteins gasdermin D (GSDMD), which are cleaved by caspase enzymes to form oligomers. These oligomers are then inserted into the cell surface membrane, causing pores to consequently result in rapid cell death. Pyroptosis, in conjunction with immunotherapy, represents a promising avenue for prognostication and antitumor therapy, providing a more precise direction for disease treatment. To gain deeper insight into the mechanisms underlying pyroptosis in real-time, non-invasive and live cell imaging techniques are urgently needed. Non-invasive imaging techniques can enhance future diagnostic and therapeutic approaches for inflammatory diseases, including different types of tumors. This review article discusses various non-invasive molecular probes for detecting pyroptosis, including genetic reporters and nanomaterials. These strategies can enhance scientists' understanding of pyroptosis and help discover personalized and effective ways to treat inflammatory diseases, particularly tumors.

Noninvasive Atherosclerotic Phenotyping: The Next Frontier into Understanding the Pathobiology of Coronary Artery Disease.

PURPOSE OF REVIEW: Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease. RECENT FINDINGS: Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation.

Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

INTRODUCTION: Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. OBJECTIVE: While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. METHODS: Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. RESULTS: LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). CONCLUSION: LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

In Vivo Imaging Techniques for the Human Scalp: A Systematic Review of the Literature.

OBJECTIVE: Scalp inflammation and alopecia are distressing conditions for which patients regularly present to dermatology. Although some diagnoses can be made clinically, others require biopsy, which carries the risk of pain, infection, bleeding, and scarring. This review examines the existing literature regarding noninvasive in vivo imaging techniques and their evidence and utility in evaluating scalp pathology, with a focus on the diagnostics of hair conditions. METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines without timeframe restrictions. The PubMed and Clarivate (Web of Science) databases were searched using the terms ("imaging" OR "in-vivo imaging" OR "non-invasive imaging" OR "non-invasive in vivo imaging" "imaging," "in-vivo imaging) AND ("human scalp disorders" OR "scalp" OR "hair loss" OR "alopecia"). Peer-reviewed randomized control trials (RCTs), prospective studies, retrospective studies, and case series or reports discussing in vivo imaging of the scalp published before 2022 were selected. RESULTS: Forty-two studies were included and discussed; modalities included laser devices (n = 27), ultrasound (US) (n = 13), infrared thermography (n = 1), skin capacitance imaging (SCI), and ultraviolet light-enhanced visualization (ULEV) (n = 1). The most common laser devices used were reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and optical coherence tomography (OCT). US techniques included high-frequency US (HFUS) and US biomicroscopy (UBM). CONCLUSION: Quality imaging of the scalp in the setting of alopecic, neoplastic, and inflammatory diseases is highly sought after. Many of these noninvasive imaging techniques show promise, each with individual advantages and disadvantages in imaging-specific conditions. Ultimately, noninvasive imaging techniques may be used to optimize patient management and minimize morbidity associated with scalp biopsies.

In vivo NIR-II structured-illumination light-sheet microscopy.

Noninvasive optical imaging with deep tissue penetration depth and high spatiotemporal resolution is important to longitudinally studying the biology at the single-cell level in live mammals, but has been challenging due to light scattering. Here, we developed near-infrared II (NIR-II) (1,000 to 1,700 nm) structured-illumination light-sheet microscopy (NIR-II SIM) with ultralong excitation and emission wavelengths up to ∼1,540 and ∼1,700 nm, respectively, suppressing light scattering to afford large volumetric three-dimensional (3D) imaging of tissues with deep-axial penetration depths. Integrating structured illumination into NIR-II light-sheet microscopy further diminished background and improved spatial resolution by approximately twofold. In vivo oblique NIR-II SIM was performed noninvasively for 3D volumetric multiplexed molecular imaging of the CT26 tumor microenvironment in mice, longitudinally mapping out CD4, CD8, and OX40 at the single-cell level in response to immunotherapy by cytosine-phosphate-guanine (CpG), a Toll-like receptor 9 (TLR-9) agonist combined with OX40 antibody treatment. NIR-II SIM affords an additional tool for noninvasive volumetric molecular imaging of immune cells in live mammals.

Serial Diffusion Tensor Imaging and Rate of Ventricular Blood Clearance in Patients with Intraventricular Hemorrhage.

BACKGROUND: We developed a noninvasive biomarker to quantify the rate of ventricular blood clearance in patients with intracerebral hemorrhage and extension to the ventricles-intraventricular hemorrhage. METHODS: We performed magnetic resonance imaging in 26 patients at 1, 14, 28, and 42 days of onset and measured their hematoma volume (HV), ventricular blood volume (VBV), and two diffusion metrics: fractional anisotropy (FA), and mean diffusivity (MD). The ipasilesional ventricular cerebral spinal fluid's FA and MD were associated with VBV and stroke severity scores (National Institute of Health Stroke Scale [NIHSS]). A subcohort of 14 patients were treated with external ventricular drain (EVD). A generalized linear mixed model was applied for statistical analysis. RESULTS: At day 1, the average HVs and NIHSS scores were 14.6 ± 16.7 cm3 and 16 ± 8, respectively. A daily rate of 2.1% and 1.3% blood clearance/resolution were recorded in HV and VBV, respectively. Ipsilesional ventricular FA (vFA) and ventricular MD (vMD) were simultaneously decreased (vFA = 1.3% per day, posterior probability [PP] > 99%) and increased (vMD = 1.5% per day, PP > 99%), respectively. Patients with EVD exhibited a faster decline in vFA (1.5% vs. 1.1% per day) and an increase in vMD (1.8% vs. 1.5% per day) as compared with patients without EVD. Temporal change in vMD was associated with VBV; a 1.00-cm3 increase in VBV resulted in a 5.2% decrease in vMD (PP < 99%). VBV was strongly associated with NIHSS score (PP = 97-99%). A larger cerebral spinal fluid drained volume was associated with a greater decrease (PP = 83.4%) in vFA, whereas a smaller volume exhibited a greater increase (PP = 94.8%) in vMD. CONCLUSIONS: In conclusion, vFA and vMD may serve as biomarkers for VBV status.

Confocal microscopy and optical coherence tomography of inflammatory skin diseases in hairs and pilosebaceous units: A systematic review.

Common skin disorders such as acne vulgaris, rosacea and folliculitis are bothersome prevalent inflammatory diseases of hair follicles that can easily be investigated bedside using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) with micrometre resolution, opening a novel era for high-resolution hair follicle diagnostics and quantitative treatment evaluation. EMBASE, PubMed and Web of Science were searched until 5 January 2023 to identify all studies imaging hair follicle characteristics by RCM and OCT for diagnosis and monitoring of treatment in hair follicle-based skin disorders. This study followed PRISMA guidelines. After inclusion of articles, methodological quality was assessed using the QUADAS-2 critical appraisal checklist. Thirty-nine in vivo studies (33 RCM and 12 OCT studies) were included. The studies focused on acne vulgaris, rosacea, alopecia areata, hidradenitis suppurativa, folliculitis, folliculitis decalvans, lichen planopilaris, discoid lupus erythemasus, frontal fibrosing alopecia and keratosis pilaris. Inter- and perifollicular morphology including number of demodex mites, hyperkeratinization, inflammation and vascular morphology could be assessed by RCM and OCT in all included skin disorders. Methodological study quality was low, and interstudy outcome variability was high. Quality assessment showed high or unclear risk of bias in 36 studies. Both RCM and OCT visualize quantitative features as size, shape, content and abnormalities of hair follicles, and have potential to support clinical diagnosis and evaluate treatment effects. However, larger studies with better methodological quality are needed to implement RCM and OCT directly into clinical practice.

Noninvasive imaging exploration of phacomatosis pigmentokeratotica using high-frequency ultrasound and optical coherence tomography: Can biopsy of PPK patients be avoided?

BACKGROUND: Phacomatosis pigmentokeratotica (PPK) is a distinct and rare type of epidermal nevus syndrome characterized by coexisting nonepidermolytic organoid sebaceous nevus (SN) with one or more speckled lentiginous nevi (SLN). Atypical nevi including compound Spitz and compound dysplastic may manifest within regions of SLN. Patients with PPK, or similar atypical nevus syndromes, may be subject to a significant lifetime number of biopsies, leading to pain, scarring, anxiety, financial burden, and decreased quality of life. The current literature includes case reports, genetics, and associated extracutaneous symptoms of PPK, but use of noninvasive imaging techniques have not been explored. We aim to investigate the value of high-frequency ultrasound (HFUS) and optical coherence tomography (OCT) in discriminating morphological features of pigmented lesions and nevus sebaceous within one patient with PPK. MATERIALS AND METHODS: Two modalities, (1) HFUS imaging, based on acoustic properties and (2) OCT imaging, based on optical properties, were used to image a patient with PPK. Benign pigmented lesions, which may raise clinical suspicion for significant atypia, and nevus sebaceous, were selected on different areas of the body to be studied. RESULTS: Five pigmented lesions and one area of nevus sebaceous were imaged and analyzed for noninvasive features. Distinct patterns of hypoechoic features were seen on HFUS and OCT. CONCLUSION: HFUS provides a deep view of the tissue, with ability to differentiate gross structures beneath the skin. OCT provides a smaller penetration depth and a higher resolution. We have described noninvasive features of atypical nevi and nevus sebaceous on HFUS and OCT, which indicate benign etiology.

Imaging of heart disease in women: review and case presentation.

Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Although major diagnostic and therapeutic advances have significantly improved the prognosis of patients with CVD in the past decades, these advances have less benefited women than age-matched men. Noninvasive cardiac imaging plays a key role in the diagnosis of CVD. Despite shared imaging features and strategies between both sexes, there are critical sex disparities that warrant careful consideration, related to the selection of the most suited imaging techniques, to technical limitations, and to specific diseases that are overrepresented in the female population. Taking these sex disparities into consideration holds promise to improve management and alleviate the burden of CVD in women. In this review, we summarize the specific features of cardiac imaging in four of the most common presentations of CVD in the female population including coronary artery disease, heart failure, pregnancy complications, and heart disease in oncology, thereby highlighting contemporary strengths and limitations. We further propose diagnostic algorithms tailored to women that might help in selecting the most appropriate imaging modality.

Evaluation of a PEGylated Fibroblast Growth Factor 21 Variant Using Novel Preclinical Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Mouse Model of Nonalcoholic Steatohepatitis.

BACKGROUND: Treatments for nonalcoholic steatohepatitis (NASH) are urgently needed. Hepatic fat fraction and shear stiffness quantified by magnetic resonance imaging (MRI-HFF) and magnetic resonance elastography (MRE-SS), respectively, are biomarkers for hepatic steatosis and fibrosis. PURPOSE: This study assessed the longitudinal effects of fibroblast growth factor 21 variant (polyethylene glycol [PEG]-FGF21v) on MRI-HFF and MRE-SS in a NASH mouse model. STUDY TYPE: Preclinical. ANIMAL MODEL: This study included a choline-deficient, amino acid-defined, high-fat diet (CDAHFD) model and 6-week-old, male C57BL/6J mice (N = 78). FIELD STRENGTH/SEQUENCE: This study was performed using: 3T: gradient-echo two-point Dixon and spin-echo (SE) echo-planar imaging elastography (200 Hz) and 7T: SE two-point Dixon and SE elastography (200 Hz). ASSESSMENT: MRI and MRE were performed before control diet (CD) or CDAHFD (BD), before PEG-FGF21v dosing (baseline), and after PEG-FGF21v treatment (WK4/8). Regions of interest for MRI-HFF and MRE-SS were delineated by J.L. and H.T. (>5 years of experience each). Fibrosis and steatosis were measured histologically after picrosirius red and H&E staining. Alkaline phosphatase, alanine transaminase, bile acids, and triglycerides (TGs) were measured. STATISTICAL TESTS: Two-tailed Dunnett's tests were used for statistical analysis; untreated CDAHFD or baseline was used for comparisons. Imaging and histology/biochemistry data were determined using Spearman correlations. Bayesian posterior distributions for MRE-SS at WK8, posterior means, and 95% credible intervals were presented. RESULTS: CDAHFD significantly increased baseline MRI-HFF (3T: 21.97% ± 0.29%; 7T: 40.12% ± 0.35%) and MRE-SS (3T: 1.25 ± 0.02; 7T: 1.78 ± 0.06 kPa) vs. CD (3T: 3.45% ± 0.7%; 7T: 12.06% ± 1.4% and 3T: 1.01 ± 0.02; 7T: 0.89 ± 0.06 kPa). At 7T, PEG-FGF21v significantly decreased MRI-HFF (WK4: 28.97% ± 1.22%; WK8: 20.93% ± 1.15%) and MRE-SS (WK4: 1.57 ± 0.04; WK8: 1.36 ± 0.05 kPa) vs. untreated (WK4: 36.36% ± 0.62%; WK8: 30.58% ± 0.81% and WK4: 2.03 ± 0.06; WK8: 2.01 ± 0.04 kPa); 3T trends were similar. WK8 SS posterior mean percent attenuation ratios (RDI ) were -68% (-90%, -44%; 3T) and -64% (-78%, -52%; 7T). MRI-HFF was significantly correlated with H&E (3T, r = 0.93; 7T, r = 0.94) and TGs (both, r = 0.92). DATA CONCLUSIONS: MRI-HFF and MRE-SS showed PEG-FGF21v effects on hepatic steatosis and fibrosis across 3 and 7T, consistent with histological and biochemical data. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Network Meta-Analysis: Noninvasive Imaging Modalities for Identifying Clinically Significant Portal Hypertension.

BACKGROUND: Although measurement of the hepatic venous pressure gradient (HVPG) is the current reference standard for obtaining portal venous pressures, several noninvasive imaging-based modalities have been proposed as alternatives. AIMS: We performed a systematic review and meta-analysis to compare the diagnostic accuracy of noninvasive imaging approaches for identifying clinically significant portal hypertension (CSPH). METHODS: Two independent reviewers conducted a literature search of PubMed, SCOPUS, and the Cochrane Library from inception until January 5, 2021. The following imaging modalities were compared to HVPG: computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance elastography, ultrasound, transient elastography (TE), shear wave elastography (SWE), acoustic radiation force impulse (ARFI) imaging, contrast-enhanced ultrasound (CEUS), and subharmonic-aided pressure estimation (SHAPE). Sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for summary receiver operating characteristic were calculated using both frequentist random effects and Bayesian network meta-analytic approaches. RESULTS: We analyzed 45 studies of 5678 patients. A broad overlapping confidence interval (CI) of DOR was observed among different imaging modalities: ARFI (30.5; 95% CI 12.7-73.3), CEUS and SHAPE (21.1; 95% CI 6.4-69.8), TE of liver stiffness (21.1; 95% CI 13.3-33.5), CT and MRI (13.7; 95% CI 7.40-25.4), SWE of liver stiffness (10.5; 95% CI 5.2-21.1), and ultrasound (9.5; 95% CI 4.9-18.4). The AUC of all imaging methods exceeded 0.8, indicating very good performance. At a cutoff of 80% specificity, TE, CEUS, and SHAPE exceeded 80% sensitivity. CONCLUSION: Overall, noninvasive imaging modalities perform well for identifying CSPH. Clinicians should consider these noninvasive and cost-efficient tests when diagnosing CSPH.

In vivo examination of healthy human skin after short-time treatment with moisturizers using confocal Raman spectroscopy and optical coherence tomography: Preliminary observations.

Skin is our barrier against environmental damage. Moisturizers are widely used to increase hydration and barrier integrity of the skin; however, there are contrasting observations on their in vivo effects in real-life settings. In cosmetic studies, corneometers and tewameters are traditionally used to assess skin hydration. In this study, two novel noninvasive diagnostic techniques, optical coherence tomography (OCT) and confocal Raman spectroscopy, were used to analyze stratum corneum and epidermal thickness (ET), water content, blood flow in function of depth, skin roughness, attenuation coefficient, natural moisturizing factor, ceramides and free fatty acids, cholesterol, urea, and lactates in 20 female subjects aged between 30 and 45 before and after 2 weeks application of a commercially available moisturizing lotion on one forearm. The untreated forearm served as control. A third measurement was conducted 1 week after cessation of moisturizing to verify whether the changes in the analyzed parameters persisted. We noticed a reduction in skin roughness, an increase in ceramides and free fatty acids and a not statistically significant increase in ET. As a conclusion, short time moisturizing appears insufficient to provide significant changes in skin morphology and composition, as assessed by OCT and RS. Novel noninvasive imaging methods are suitable for the evaluation of skin response to topical moisturizers. Further studies on larger sample size and longer treatment schedules are needed to analyze changes under treatment with moisturizers and to standardize the use of novel noninvasive diagnostic techniques.

Utility of high-resolution ultrasound in measuring subcutaneous fat thickness.

OBJECTIVE: Previous studies conclude that high-resolution ultrasound (HRUS) enables noninvasive and accurate measurements of subcutaneous fat thickness. The primary objective of this cross-sectional study was to better characterize subcutaneous fat thickness measurements in a diverse patient population using HRUS. Secondarily, we sought to correlate these measurements with patients' body image. METHODS: A cross-sectional study to measure subcutaneous fat measurements at seven distinct anatomic sites, including upper and lower extremities, submental, and torso regions, in 40 men and women of different ages and races using HRUS. Independent t-tests and analysis of variance were performed to analyze findings. RESULTS: In our patient population, on average, women had thicker subcutaneous fat than men at all anatomic sites. Asian patients had significantly reduced fat thickness at peripheral anatomic sites, such as arms when compared to patients who identified as Black and Other (p = 0.05 and p = 0.008, respectively). Lastly, women reported decreased total body satisfaction at all anatomic sites when compared to men. CONCLUSION: The information obtained and methods developed in this study may be utilized clinically during patient selection for fat reduction procedures, including for estimating the degree of likely benefit; for managing pathologies involving subcutaneous fat thickness alteration; and to monitor the progression of lipodystrophy secondary to disease or drugs.

Transforming the treatment of psoriasis to the 21st century: Detecting subclinical therapeutic response to secukinumab using optical coherence tomography as a prognostic indicator.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive imaging device that scans the skin up to 2 mm in depth. OCT can capture real-time epidermal thickness (ET) measurements and detect subclinical changes in inflammatory skin diseases like eczema and psoriasis. © 2022 Wiley Periodicals LLC. OBJECTIVE: To determine if measuring ET with OCT can detect a subclinical therapeutic response in psoriasis treated with the biological therapy, secukinumab (an IL-17A antagonist). DESIGN: Phase IV, single-center, open-label, and single-arm study. PARTICIPANTS: Twenty-six consecutive patients with moderate to severe plaque psoriasis. MEASUREMENTS: Clinical, dermoscopic, and OCT images were obtained at each visit. The clinician measured disease severity with the Investigator's Global Assessment (IGA) and Psoriasis Area And Severity Index (PASI). OCT was used to scan the ET at the center of lesional skin (ET-L), along the border, and normal skin (ET-N) on the same body plane; their difference was noted as ΔET. RESULTS: Initially, ET-L was greater than ET-N (p < 0.0001), their differences decreased throughout the study, and there were no significant differences at Week 16 (p = 0.48). Twenty-four (92%) patients achieved a 50% reduction in PASI score (PASI50); they had lower ΔET at Weeks 0, 1, 3, 4, and 8 compared to those who did not clear (p < 0.04). Having a lower ΔET at Week 4 was associated with a shorter time to reach PASI50 (p = 0.02). CONCLUSION: ET measurements using OCT can detect an early subclinical response to secukinumab compared to clinical scoring and identify nonresponders as early as 4 weeks.

Diagnostic performance of CMR, SPECT, and PET imaging for the detection of cardiac amyloidosis: a meta-analysis.

BACKGROUND: Noninvasive myocardial imaging modalities, such as cardiac magnetic resonance (CMR), single photon emission computed tomography (SPECT), and Positron emission tomography (PET), are well-established and extensively used to detect cardiac amyloid (CA). The purpose of this study is to directly compare CMR, SPECT, and PET scans in the diagnosis of CA, and to provide evidence for further scientific research and clinical decision-making. METHODS: PubMed, Embase, and Cochrane Library were searched. Studies used CMR, SPECT and/or PET for the diagnosis of CA were included. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), their respective 95% confidence intervals (CIs) and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated. Quality assessment of included studies was conducted. RESULTS: A total of 31 articles were identified for inclusion in this meta-analysis. The pooled sensitivities of CMR, SPECT and PET were 0.84, 0.98 and 0.78, respectively. Their respective overall specificities were 0.87, 0.92 and 0.95. Subgroup analysis demonstrated that 99mTc-HMDP manifested the highest sensitivity (0.99). 99mTc-PYP had the highest specificity (0.95). The AUC values of 99mTc-DPD, 99mTc-PYP, 99mTc-HMDP were 0.89, 0.99, and 0.99, respectively. PET scan with 11C-PIB demonstrated a pooled sensitivity of 0.91 and specificity of 0.97 with an AUC value of 0.98. CONCLUSION: Our meta-analysis reveals that SEPCT scans present better diagnostic performance for the identification of CA as compared with other two modalities.

Feasibility study of 68Ga-labeled CAR T cells for in vivo tracking using micro-positron emission tomography imaging.

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used 68Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by 68Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89Zr and 68Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of 68Ga-labeled CAR T cells is only one twenty-fourth of 89Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68Ga instead of 89Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.

The value of multimodality imaging in diagnosis and treatment of cardiac lipoma.

BACKGROUND: Cardiac lipoma is a rare primary tumor in the heart and pericardium. Multimodality imaging methods, especially magnetic resonance imaging (MRI), are crucial in detecting and diagnosing cardiac lipomas. Besides, they are of significant importance in management of cardiac lipomas. The aim of this study was to evaluate the value of multimodality imaging methods in diagnosing and treatment of cardiac lipoma by describing a series of cases of cardiac lipoma. MATERIALS AND METHODS: Data of patients with cardiac lipoma at a local institution were retrospectively collected. Their imaging findings on echocardiography, computed tomography (CT), and cardiac MRI and clinical management were described in detail. RESULTS: 12 patients with cardiac lipoma were retrospectively included with thirteen lipomas found within heart and pericardium. Two patients' lipoma were symptomatic, while lipomas in other 10 patients were found incidentally. Most lipomas were sensitively detected with echocardiography. Accurate diagnoses were achieved with CT and MRI in all cases. Surgical resection was performed in one symptomatic patient due to the obstruction of the left ventricular outflow tract, while the removal of pericardial lipoma in another symptomatic patient was not possible due to diffuse myocardial infiltration observed in MRI. Based on MRI findings, two patients without clinical symptoms also underwent surgery to prevent the risk of detachment of ventricular lipoma with a narrow pedicle in one patient and potential further thinning of the myocardium by pericardial lipoma growth in another patient. CONCLUSIONS: Cardiac lipoma could be sensitively detected and accurately diagnosed with multiple noninvasive imaging tools. Comprehensive evaluation with multimodality imaging methods should also be conducted for better management planning and follow-up in all patients.

Reflectance Confocal Microscopy, Optical Coherence Tomography, and Multiphoton Microscopy in Inflammatory Skin Disease Diagnosis.

BACKGROUND AND OBJECTIVES: Technological advances in medicine have brought about many novel skin imaging devices. This review aims to evaluate the scientific evidence supporting the use of noninvasive optical imaging techniques to aid in the diagnosis and prognosis of inflammatory skin diseases. STUDY DESIGN/MATERIALS AND METHODS: PubMed and Scopus were searched in September 2020 according to PRISMA guidelines for articles using reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and multiphoton microscopy (MPM) in inflammatory skin diseases, excluding studies monitoring treatment efficacy. RESULTS: At the time of the study, there were 66 articles that addressed the utilization of noninvasive imaging in interface, spongiotic, psoriasiform, vesiculobullous, and fibrosing/sclerosing inflammatory skin dermatoses: RCM was utilized in 46, OCT in 16, and MPM in 5 articles. RCM was most investigated in psoriasiform dermatoses, whereas OCT and MPM were both most investigated in spongiotic dermatoses, including atopic dermatitis and allergic contact dermatitis. CONCLUSIONS: There is preliminary evidence to support the diagnostic potential of noninvasive optical imaging techniques in inflammatory skin diseases. Improvements in the devices and further correlation with histology will help broaden their utility. Additional studies are needed to determine the parameters for diagnostic features, disease differentiation, and staging of inflammatory skin conditions. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.