Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

Nerve Injury Following Regional Nerve Block: A Literature Review of Its Etiologies, Risk Factors, and Prevention.

PURPOSE OF REVIEW: Postoperative nerve injury after nerve block is complex and multifactorial. The mechanisms, etiologies, and risk factors are explored. This review article conducts a literature search and summarizes current evidence and best practices in prevention of nerve injury. RECENT FINDINGS: Emerging technology such as ultrasound, injection pressure monitors, and nerve stimulators for peripheral nerve block have been incorporated into regular practice to reduce the rate of nerve injury. Studies show avoidance of intrafascicular injection, limiting concentrations/volumes of local anesthetic, and appropriate patient selection are the most significant controllable factors in limiting the negative consequences of nerve block. Peripheral nerve injury is an uncommon occurrence after nerve block and is obscured by surgical manipulation, positioning, and underlying neural integrity. Underlying neural integrity is not always evident despite an adequate history and physical exam. Surgical stress, independently of nerve block, may exacerbate these neurologic disease processes and make diagnosing a postoperative nerve injury more challenging. Prevention of nerve injury by surgical teams, care with positioning, and avoidance of intrafascicular injection with nerve block are the most evidence-based practices.

MRI-based Neuropathy Score Reporting And Data System (NS-RADS): multi-institutional wider-experience usability study of peripheral neuropathy conditions among 32 radiology readers.

OBJECTIVE: To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. METHODS: This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger's kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. RESULTS: Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1-88.8%) and trainees, 86.6% (95% CI 85.2-87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) (p = 0.036). CONCLUSION: Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. CLINICAL RELEVANCE STATEMENT: The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. KEY POINTS: • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively).

Association of plexiform and diffuse neurofibromas with malignant peripheral nerve sheath tumor in NF I patients: a whole-body MRI assessment.

OBJECTIVE: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs). MATERIALS AND METHODS: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs. RESULTS: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis. CONCLUSION: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors.

Comparison between ZOOMit DWI and conventional DWI in the assessment of foot and ankle infection: a prospective study.

OBJECTIVE: The study aimed to compare ZOOMit diffusion-weighted imaging (DWI) MRI with conventional DWI MRI for visualizing small bones in the foot, soft tissue abscesses, and osteomyelitis. MATERIALS AND METHODS: The cohort consisted of a consecutive series of patients with potential foot and ankle infections referred for MR imaging. Patients were imaged using both conventional and ZOOMit DWI in the same setting. Blinded reads were then conducted in separate settings and independent of known clinical diagnosis by two expert radiologists. The results from the reads were compared statistically using paired t-tests and with biopsy specimen analysis, both anatomopathological and microbiological. RESULTS: There was improvement in fat suppression using ZOOMit sequence compared to conventional DWI (p = .001) with no significant difference in motion artifacts (p = .278). ZOOMit had a higher rate of concordance with pathology findings for osteomyelitis (72%, 31/43 cases) compared with conventional DWI (60%, 26/43 cases). ZOOMit also identified 46 additional small bones of the foot and ankle (405/596, 68.0%) than conventional DWI (359/596, 60.2%). Conventional DWI however exhibited a more negative contrast-to-noise ratio (CNR) than ZOOMit (p = 0.001). CONCLUSION: ZOOMit DWI improves distal extremity proton diffusion assessment and helps visualize more bones in the foot, with less image distortion and improved fat saturation at the expense of reduced CNR. This makes it a viable option for assessing lower extremity infections. CLINICAL RELEVANCE STATEMENT: This study highlights the novel utilization of ZOOMit diffusion-weighted imaging (DWI) for the assessment of lower extremity lesions compared to conventional DWI. KEY POINTS: • Distal extremity diffusion-weighted imaging (DWI) is often limited. • ZOOMit DWI displayed improved fat suppression with less motion artifacts and better visualization of the lower extremity bones than conventional DWI. • ZOOMit shows decreased contrast-to-noise ratio than conventional DWI.

Predictive Value of Radiographic and Magnetic Resonance Imaging Characteristics on Patient Outcomes in Confirmed Acute Osteomyelitis of the Extremities.

OBJECTIVE: The aim of this study was to determine whether imaging characteristics on plain radiography, magnetic resonance imaging (MRI), and diffusion-weighted imaging are predictive of patient outcomes in cases of confirmed osteomyelitis (OM). MATERIALS AND METHODS: In this cross-sectional study, 3 experienced musculoskeletal radiologists evaluated pathologically proven cases of acute extremity OM and recorded imaging characteristics on plain radiographs, MRI, and diffusion-weighted imaging. These characteristics were then compared with the patient outcomes after a 3-year follow-up using length of stay, amputation-free survival, readmission-free survival, and overall survival using multivariate Cox regression analysis. Hazard ratio and corresponding 95% confidence intervals are reported. False discovery rate-adjusted P values were reported. RESULTS: For the 75 consecutive cases of OM in this study, multivariate Cox regression analysis adjusting for sex, race, age, body mass index, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count showed no correlation among any of the recorded characteristics on imaging and patient outcomes. Despite the high sensitivity and specificity of MRI for diagnosing OM, there was no correlation between MRI characteristics and patient outcomes. Furthermore, patients with coexistent abscess of the soft tissue or bone with OM had comparable outcomes using the previously mentioned metrics of length of stay, amputation-free survival, readmission-free survival, and overall survival. CONCLUSION: Neither radiography nor MRI features predict patient outcomes in extremity OM.

Diffusion weighted imaging of extremity bone tumors-inter-reader analysis and incremental value over conventional MR imaging.

OBJECTIVE: To determine whether the addition of diffusion-weighted imaging (DWI) to conventional MRI improves diagnostic accuracy of bone tumor characterization with the hypothesis that the DWI has incremental value in the diagnosis of osseous tumors. METHODS: In this multireader cross-sectional validation study, four musculoskeletal radiologists evaluated osseous tumors blinded to final diagnosis in two rounds-first without DWI or apparent diffusion coefficient (ADC) maps, then months later with these available. Each reader recorded a binary result as to whether the lesion is benign or malignant. Intraclass correlation (ICC) and Conger's κ were used. Diagnostic performance measures including area under the receiver operating curve (AUC) were reported. RESULTS: 133 osseous tumors of the extremities (76 benign, 57 malignant) were tested. Blinded to DWI, average reader sensitivity, specificity, positive-predictive value, and negative-predictive value were 0.83, 0.92, 0.94, and 0.82, respectively. With DWI, the values were 0.85, 0.92, 0.94, and 0.83, respectively. Interreader agreement was good for both rounds (0.67 and 0.71, respectively, p-value > 0.05). Average reader confidence was 4.1 and 4.4, respectively (p-value < 0.001). ADC values and DWI/ADC ratios showed significant differences between benign and malignant tumors. CONCLUSION: DWI and ADC show statistically significantly different values of benign from malignant osseous tumors and mildly increased radiologist confidence with similar interreader reliability. However, given similar diagnostic accuracy, conventional MR imaging is adequate for bone tumor characterization and incremental value of DWI is limited. ADVANCES IN KNOWLEDGE: This paper is the first of its kind to report the use of DWI/ADC ratio for the diagnosis of bone tumors.

Diagnostic performance comparison of conventional radiography to magnetic resonance imaging for suspected osteomyelitis of the extremities: a multi-reader study.

OBJECTIVE: To determine whether MRI provides improved diagnostic accuracy compared to radiography for the diagnosis of extremity osteomyelitis (OM) with multi-reader analysis. METHODS: In this cross-sectional study, three musculoskeletal fellowship-trained expert radiologists evaluated cases of suspected OM in two rounds-first using radiographs (XR), then with conventional MRI. Radiologic features consistent with OM were recorded. Each reader recorded individual findings on both modalities and rendered a binary diagnosis along with certainty of final diagnosis on a confidence scale of 1-5. This was compared with the pathology-proven diagnosis of OM to determine diagnostic performance. Intraclass correlation (ICC) and Conger's Kappa were used for statistics. RESULTS: XR and MRIs of 213 pathology proven cases (51.5 years ± 14.0 years, mean ± St.Dev.) were included in this study, with 79 tested positive for OM and 98 were positive for a soft tissue abscess, with 78 patients being negative for both. In total, 139 were males and 74 females with bones of interest in the upper and lower extremities in 29 and 184 cases, respectively. MRI showed significantly higher sensitivity and negative predictive value than XR (p < 0.001 for both metrics). Conger's Kappa for OM diagnosis were 0.62 and 0.74 on XR and MRI, respectively. Reader confidence improved slightly from 4.54 to 4.57 when MRI was used. CONCLUSIONS: MRI is a diagnostically more effective imaging modality than XR for finding extremity osteomyelitis with better inter-reader reliability. CLINICAL RELEVANCE STATEMENT: This study validates the diagnosis of OM with MRI over XR but adds novelty because it is the largest study of its kind with a clear reference standard to guide clinician decision making. KEY POINTS: • Radiography is the first-line imaging modality for musculoskeletal pathology but MRI can add value for infections. • MRI shows greater sensitivity for the diagnosis of osteomyelitis of the extremities than radiography. • This improved diagnostic accuracy makes MRI a better imaging modality for patients with suspected osteomyelitis.

Incremental value of diffusion weighted imaging over conventional MRI for the diagnosis of osteomyelitis of extremities.

OBJECTIVE: To determine the incremental value of diffusion weighted imaging (DWI) over conventional MR imaging in diagnosing extremity osteomyelitis (OM). MATERIALS AND METHODS: In this cross-sectional study, three experienced musculoskeletal radiologists evaluated clinically suspected cases of extremity OM in two rounds-first on conventional MR imaging, and then conventional MR imaging combined with DWI 4-6 weeks later. The readers recorded a result of the presence or absence of OM and their diagnostic confidence on a 1-5 scale. Mean and minimum apparent diffusion coefficient (ADC) were measured. Pathology diagnosis served as the reference standard. Statistical analysis utilized intraclass correlation (ICC) and Conger's kappa. RESULTS: A total of 213 scans of suspected OM were reviewed by three musculoskeletal radiologists with no significant changes in sensitivity (0.97, 0.97), specificity (0.97, 0.94), positive predictive value (0.91, 0.87), or negative predictive value (0.98, 0.98) between conventional MR imaging and MR imaging combined with DWI, respectively. Reader confidence did not significantly change with the addition of DWI (4.55 and 4.70, respectively). A high inter-reader agreement was observed for the diagnosis of OM, soft tissue abscess, and intraosseous abscess in both rounds. A higher mean (1.46+/-0.43 × 10-3 mm2/s > 0.64+/-0.47 × 10-3mm2/s) and minimum (1.18+/-0.45 × 10-3mm2/s > 0.37+/-0.44 × 10-3mm2/s) ADC value was associated with OM (p-value < 0.0001) with odds ratios of 1.34 and 1.31, respectively, for mean and minimum ADC of the involved bone. CONCLUSION: DWI-derived ADC increase is associated with OM. The use of DWI slightly increases reader confidence in the diagnosis of OM; however, no significant incremental value over conventional MR imaging is seen for the final diagnosis of OM.

Chilaiditi Sign in a Patient With Acute Coronary Syndrome: A Case Report.

Chilaiditi sign is a radiographic finding where part of the colon is found to be between the diaphragm and liver. Chilaiditi syndrome is characterized by symptoms such as chest or abdominal pain and shortness of breath once Chilaiditi sign is found on imaging. Chilaiditi sign is typically diagnosed by CT angiography (CTA) scan although it can also be seen on X-ray imaging at times. In most cases, Chilaiditi sign does not require acute intervention, as will be seen in our patient; however, it is important to include it in the differential diagnosis when a patient presents with characteristic symptoms. We present a case of a 71-year-old female who presented with chest pressure and shortness of breath due to acute coronary syndrome; however, she was found to have Chilaiditi sign, which was diagnosed by CTA chest.

Osseous-Tissue Tumor Reporting and Data System With Diffusion-Weighted Imaging of Bone Tumors-An Interreader Analysis and Whether It Adds Incremental Value on Tumor Grading Over Conventional Magnetic Resonance Imaging.

OBJECTIVE: The aim of the study is to determine whether the use of diffusion-weighted imaging (DWI) provides incremental increase in performance in the osseous-tissue tumor reporting and data system (OT-RADS) with the hypothesis that use of DWI improves interreader agreement and diagnostic accuracy. METHODS: In this multireader cross-sectional validation study, multiple musculoskeletal radiologists reviewed osseous tumors with DW images and apparent diffusion coefficient maps. Four blinded readers categorized each lesion using the OT-RADS categorizations. Intraclass correlation (ICC) and Conger κ were used. Diagnostic performance measures including area under the receiver operating curve were reported. These measures were then compared with the previously published work that validated OT-RADS but did not include incremental value assessment of DWI. RESULTS: One hundred thirty-three osseous tumors of the upper and lower extremities (76 benign, 57 malignant) were tested. Interreader agreement for OT-RADS with DWI (ICC = 0.69) was slightly lower (not statistically different) from the previously published work that did not incorporate DWI (ICC = 0.78, P > 0.05). The mean sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve including DWI of the 4 readers were 0.80, 0.95, 0.96, 0.79, and 0.91, respectively. In the previously published work without DWI, the mean values of the readers were 0.96, 0.79, 0.78, 0.96, and 0.94, respectively. CONCLUSIONS: The addition of DWI to the OT-RADS system does not allow significantly improved area under the curve diagnostic performance measure. Conventional magnetic resonance imaging can be prudently used for OT-RADS for reliable and accurate characterization of bone tumors.

Establishing a Robust and Reliable Response from a Potent Osmium-Based Photosensitizer Via Lipid Nanoformulation†.

Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac-[Os(phen)2 (IP-4T)](Cl)2 , referred to as ML18J03 herein, with light EC50 values as low as 20 pm. ML18J03 also exhibits low dark toxicity and submicromolar light EC50 values in hypoxia in some cell lines. However, owing to its longer oligothiophene chain, ML18J03 is not completely water soluble and forms 1-2 µm sized aggregates in PBS containing 1% DMSO. This aggregation causes variability in PDT efficacy between assays and thus unreliable and irreproducible reports of in vitro activity. To that end, we utilized PEG-modified DPPC liposomes (138 nm diameter) and DSPE-mPEG2000 micelles (10.2 nm diameter) as lipid nanoformulation vehicles to mitigate aggregation of ML18J03 and found that the spectroscopic properties important to biological activity were maintained or improved. Importantly, the lipid formulations decreased the interassay variance between the EC50 values by almost 20-fold, with respect to the unformulated ML18J03 when using broadband visible light excitation (P = 0.0276). Herein, lipid formulations are presented as reliable platforms for more accurate in vitro photocytotoxicity quantification for PSs prone to aggregation (such as ML18J03) and will be useful for assessing their in vivo PDT effects.

Diffusion-weighted MR imaging of musculoskeletal tissues: incremental role over conventional MR imaging in bone, soft tissue, and nerve lesions.

Diffusion-weighted imaging is increasingly becoming popular in musculoskeletal radiology for its incremental role over conventional MR imaging in the diagnostic strategy and assessment of therapeutic response of bone and soft tissue lesions. This article discusses the technical considerations of diffusion-weighted imaging, how to optimize its performance, and outlines the role of this novel imaging in the identification and characterization of musculoskeletal lesions, such as bone and soft tissue tumors, musculoskeletal infections, arthritis, myopathy, and peripheral neuropathy. The readers can use the newly learned concepts from the presented material containing illustrated case examples to enhance their conventional musculoskeletal imaging and interventional practices and optimize patient management, their prognosis, and outcomes.

Acetabular paralabral cysts demonstrating perineural propagation.

OBJECTIVE: Acetabular paralabral cysts are common and are almost always associated with labral tears. Uncommonly, they extend into the periacetabular soft tissues or may propagate along peripheral nerves causing pain and hip dysfunction. The aim was to evaluate the clinical and MRI presentations of such cases including perineural propagation. METHODS: Retrospective cross-sectional study with a search of electronic health records for cases of acetabular paralabral cysts demonstrating perineural propagation was performed. Clinical and MR imaging features were tabulated after re-review by experienced musculoskeletal radiologists, and available outcomes were recorded. Descriptive statistics were performed. RESULTS: 14 cases were recorded. The mean age was 56.9 years (range = 30-79 years) and female:male ratio was 1:2.6. The commonest presenting complaint was hip pain (10/14, 71.4%). Other complaints included groin pain, perineal pain and hip dysfunction. No symptoms were attributed to the acetabular paralabral cyst in 3/14 patients (21.4%). None had foot drop. The cysts were multilocular in all cases and were homogenously T2 hyperintense in 13/14 (92.9%). Labral tears were identified in 11/14 cases (78.6%). The sciatic nerve was most commonly involved in 5/14 cases (35.7%) with the obturator, medial femoral cutaneous nerve, femoral nerve, superior and inferior gluteal nerves also affected.No intervention was undertaken in 9/14 cases (64.3%). 5/14 (35.7%) underwent image guided aspiration and corticosteroid injection. 4/5 such patients reported reduced pain following the procedure. CONCLUSION: Paralabral cysts demonstrating perineural propagation are uncommon and exhibit varied presentations. Most patients who underwent image-guided or surgical interventions reported an improvement in symptoms. ADVANCES IN KNOWLEDGE.: This is the first description of a series of patients with acetabular paralabral cysts demonstrating perineural propagation in the literature. A comprehensive description of their clinical and imaging characteristics and interventions/outcomes where relevant is provided.

Neuropathy Score Reporting and Data System (NS-RADS): MRI Reporting Guideline of Peripheral Neuropathy Explained and Reviewed.

A standardized guideline and scoring system should be used for the MR imaging diagnosis of peripheral neuropathy. The MR imaging-based Neuropathy Score Reporting and Data System (NS-RADS) is a newly devised classification system (in press in AJR) that can be used to communicate both type and severity of peripheral neuropathy in the light of clinical history and examination findings. The spectrum of neuropathic conditions and peripheral nerve disorders covered in this system includes nerve injury, entrapment, neoplasm, diffuse neuropathy, and post-interventional states. This classification system also describes the temporal MR imaging appearances of regional muscle denervation changes. This review article is based on the multicenter validation study pre-published in American journal of Roentgenology and discusses technical considerations of optimal MR imaging for peripheral nerve evaluation and discusses the NS-RADS classification and its severity scales with illustration of conditions that fall under each classification. The readers can gain knowledge of the NS-RADS classification system and learn to apply it in their practices for improved inter-disciplinary communications and timely patient management.

Deep-Tissue Activation of Photonanomedicines: An Update and Clinical Perspectives.

With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies.

Neuropathy Score Reporting and Data System: A Reporting Guideline for MRI of Peripheral Neuropathy With a Multicenter Validation Study.

BACKGROUND. A standardized guideline and scoring system would improve evaluation and reporting of peripheral neuropathy (PN) on MRI. OBJECTIVE. The objective of this study was to create and validate a neuropathy classification and grading system, which we named the Neuropathy Score Reporting and Data System (NS-RADS). METHODS. This retrospective study included 100 patients with nerve imaging studies and known clinical diagnoses. Experts crafted NS-RADS using mutually agreed-on qualitative criteria for the classification and grading of PN. Different classes were created to account for the spectrum of underlying pathologies: unremarkable (U), injury (I), neoplasia (N), entrapment (E), diffuse neuropathy (D), not otherwise specified (NOS), and postintervention state (PI). Subclasses were established to describe the severity or extent of the lesions. Validation testing was performed by 11 readers from 10 institutions with experience levels ranging from 3 to 18 years after residency. After initial reader training, cases were presented to readers who were blinded to the final clinical diagnoses. Interobserver agreement was assessed using correlation coefficients and the Conger kappa, and accuracy testing was performed. RESULTS. Final clinical diagnoses included normal (n = 5), nerve injury (n = 25), entrapment (n = 15), neoplasia (n = 33), diffuse neuropathy (n = 18), and persistent neuropathy after intervention (n = 4). The miscategorization rate for NS-RADS classes was 1.8%. Final diagnoses were correctly identified by readers in 71-88% of cases. Excellent inter-reader agreement was found on the NS-RADS pathology categorization (κ = 0.96; 95% CI, 0.93-0.98) as well as muscle pathology categorization (κ = 0.76; 95% CI, 0.68-0.82). The accuracy for determining milder versus more severe categories per radiologist ranged from 88% to 97% for nerve lesions and from 86% to 94% for muscle abnormalities. CONCLUSION. The proposed NS-RADS classification is accurate and reliable across different reader experience levels and a spectrum of PN conditions. CLINICAL IMPACT. NS-RADS can be used as a standardized guideline for reporting PN and improved multidisciplinary communications.

Is Tumor Cell Specificity Distinct from Tumor Selectivity In Vivo?: A Quantitative NIR Molecular Imaging Analysis of Nanoliposome Targeting.

The significance and ability for receptor targeted nanoliposomes (tNLs) to bind to their molecular targets in solid tumors in vivo has been questioned, particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity. This study presents, for the first time, in situ NIR molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors, as opposed to tumor selectivity, which includes influences of enhanced tumor permeability and retention. Results show that neither tumor delivery nor selectivity (tumor-to-normal ratio) of cetuximab and IRDye conjugated tNLs correlate with EGFR expression in U251, U87 and 9L tumors, and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%. Conversely, their in vivo specificity, which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging, correlates positively with EGFR expression levels in vitro and ex vivo (Pearson's r= 0.92 and 0.96, respectively). This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity. The findings encourage their continued adoption as platforms for precision medicine, and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.

What NIR photodynamic activation offers molecular targeted nanomedicines: Perspectives into the conundrum of tumor specificity and selectivity.

Near infrared (NIR) photodynamic activation is playing increasingly critical roles in cutting-edge anti-cancer nanomedicines, which include spatiotemporal control over induction of therapy, photodynamic priming, and phototriggered immunotherapy. Molecular targeted photonanomedicines (mt-PNMs) are tumor-specific nanoscale drug delivery systems, which capitalize on the unparalleled spatio-temporal precision of NIR photodynamic activation to augment the accuracy of tumor tissue treatment. mt-PNMs are emerging as a paradigm approach for the targeted treatment of solid tumors, yet remain highly complex and multifaceted. While ligand targeted nanomedicines in general suffer from interdependent challenges in biophysics, surface chemistry and nanotechnology, mt-PNMs provide distinct opportunities to synergistically potentiate the effects of ligand targeting. This review provides what we believe to be a much-need demarcation between the processes involved in tumor specificity (biomolecular recognition events) and tumor selectivity (preferential tumor accumulation) of ligand targeted nanomedicines, such as mt-PNMs, and elaborate on what NIR photodynamic activation has to offer. We discuss the interplay between both tumor specificity and tumor selectivity and the degree to which both may play central roles in cutting-edge NIR photoactivable nanotechnologies. A special emphasis is made on NIR photoactivable biomimetic nanotechnologies that capitalize on both specificity and selectivity phenomena to augment the safety and efficacy of photodynamic anti-tumor regimens.