Magnetic resonance imaging-guided renal biopsy shows high safety and diagnostic yield: a tertiary cancer center experience.

OBJECTIVES: To evaluate the technical success and outcomes of renal biopsies performed under magnetic resonance imaging (MRI) using a closed-bore, 1.5-Tesla MRI unit. MATERIALS AND METHODS: We retrospectively reviewed our institutional biopsy database and included 150 consecutive MRI-guided biopsies for renal masses between November 2007 and March 2020. We recorded age, sex, BMI, tumor characteristics, RENAL nephrometry score, MRI scan sequence, biopsy technique, complications, diagnostic yield, pathologic outcome, and follow-up imaging. Univariate logistic regression was used to assess the association between different parameters and the development of complications. McNemar's test was used to assess the association between paired diagnostic yield measurements for fine-needle aspiration and core samples. RESULTS: A total of 150 biopsies for 150 lesions were performed in 150 patients. The median tumor size was 2.7 cm. The median BMI was 28.3. The lesions were solid, partially necrotic/cystic, and predominantly cystic in 137, eight, and five patients, respectively. Image guidance using fat saturation steady-state free precession sequence was recorded in 95% of the biopsy procedures. Samples were obtained using both fine-needle aspiration (FNA) and cores in 99 patients (66%), cores only in 40 (26%), and FNA only in three (2%). Tissue sampling was diagnostic in 144 (96%) lesions. No major complication developed following any of the biopsy procedures. The median follow-up imaging duration was 8 years and none of the patients developed biopsy-related long-term complication or tumor seeding. CONCLUSIONS: MRI-guided renal biopsy is safe and effective, with high diagnostic yield and no major complications. CLINICAL RELEVANCE STATEMENT: Image-guided renal biopsy is safe and effective, and should be included in the management algorithm of patients with renal masses. Core biopsy is recommended. KEY POINTS: • MRI-guided biopsy is a safe and effective technique for sampling of renal lesions. • MRI-guided biopsy has high diagnostic yield with no major complications. • Percutaneous image-guided biopsy plays a key role in the management of patients with renal masses.

Modification of kitchen blenders into controllable laboratory mixers for mechanochemical synthesis of atomically thin materials.

Graphene and related two-dimensional materials (2DMs) have shown promise across numerous technology areas including flexible electronics, energy storage and pollution remediation. Research into novel applications of these atomically thin materials relies on access to synthesis techniques for producing 2DMs with suitable quality and quantity. Liquid-phase exfoliation is a mechanochemical approach that can achieve this and produce defect-free nanomaterial dispersions which are compatible for downstream use (e.g. inkjet printing, coatings). Here, using kitchen blenders to deliver shear-driven exfoliation, we develop a range of inexpensive hardware solutions that can allow researchers to synthesise 2DMs using a controllable, sustainable and scalable process. Extensive modifications were necessary as the onboard electronics lack the experimental controls (temperature, speed, characterisation) for scientific research and precision synthesis. The technical aspects (including the many lessons learned) of the modifications are discussed and a simple selection process is proposed for creating bespoke mechanochemical processors for any application in the hope that this encourages experimentation. Specific builds with detailed notes, cost breakdown and associated files are provided in the Open Science Framework (OSF) repository, OpenLPE associated with this article.

Sustainable Upcycling of Spent Electric Vehicle Anodes into Solution-Processable Graphene Nanomaterials.

A major transition to electric vehicles (EVs) is underway globally, as countries target reductions in greenhouse gas emissions from the transport sector. As this rapid growth continues, significant challenges remain around how to sustainably manage the accompanying large volumes of waste from end-of-life lithium-ion batteries that contain valuable rare earth and critical materials. Here, we show that high-shear exfoliation in aqueous surfactants can upcycle spent graphite anodes recovered from an EV into few-layer graphene dispersions. For the same hydrodynamic conditions, we report a process yield that is 37.5% higher when using spent graphite anodes as the precursor material over high-purity graphite flakes. When the surfactant concentration is increased, the average atomic layer number reduces in a similar way to that of high-purity precursors. We find that the electrical conductance of few-layer graphene produced using the graphite flake precursor is superior and identify the limitations when using aqueous surfactant solutions as the exfoliation medium for spent graphite anode material. Using these nontoxic solution-processable nanomaterial dispersions, functional paper-based electronic circuit boards were fabricated, illustrating the potential for end-to-end, environmentally sustainable upcycling of spent EV anodes into new technologies.

Siwa Oasis groundwater quality: factors controlling spatial and temporal changes.

Siwa Oasis is of great historical, environmental, and scientific importance, as it contains unique archeological and geological features. Groundwater is the main source of freshwater in that oasis. The carbonate aquifer groundwater, used for irrigation, was sampled to evaluate factors controlling quality changes spatially and temporally by applying hydrochemical and statistical analyses. The salinity of the aquifer varied spatially from 1367 to 8645 mg/l based on one hydrogeological condition, with the highest TDS (> 5432.5 mg/l, 25% of samples) at the central part of the study area. Temporally, the salinity changed slightly from 3754.3 mg/l (in 2014) to 4222.4 mg/l (in 2020). The cession of illegal wells, pumping control, and excavation of formed salts have a noticeable impact on salinity (mediate the increase in salinity) and ions. However, about 61% of the studied samples can be considered unsuitable for irrigation owing to salinity and can harm plant yield. The heavy metals studied (Fe, Mn, Cu, Pb), except Cd, were within the permissible limit for irrigation water. Finally, it is proposed to construct desalination stations to enhance water quality for irrigation in the study area and set up many companies for salt extraction.

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

Vehicle non-exhaust emissions - Revealing the pathways from source to environmental exposure.

Brakes, tyres and road deposits have become important contributors to the overall particle emissions of vehicles globally, with constituents in these wear particles considered to be harmful to human health (PM10 and PM2.5). Previous research has documented mass/size distributions, physical and chemical characteristics, emission factors and long-term implications and environmental occurrences. The complex path these pollutants take from their origins to the environment, however, is not fully understood. This is partly owing to the breadth of spatio-temporal scales involved in the advection-diffusion processes (nanometers to meters, microseconds to minutes). These short timescale particle transport mechanisms impact human exposure, such as pedestrians and cyclists, and initiate the long-term interaction of these pollutants with other environmental compartments. Here, we present an analysis for urban driving conditions to highlight the opportunities to reveal these complex pathways and formulate opinions that aim to stimulate future enquiry. We describe important vehicular areas and exposure scenarios where efforts should focus. Future interdisciplinary research into these particle transport mechanisms must be prioritised as it can provide the foundation for developing urgently needed pollution control strategies, transport infrastructure layouts and transport policies that mitigate, or possibly eliminate pollution exposure risks.

The use of laser interstitial thermal therapy in the treatment of brain metastases: a literature review.

PURPOSE: The aim of this paper is to discuss the current evidence for Laser Interstitial Thermal Therapy (LITT) in the treatment of brain metastases, our current recommendations for patient selection and the future perspectives for this therapy. We have also touched upon the possible complications and role of systemic therapy coupled with LITT for the treatment of brain metastases. MATERIAL AND METHODS: Two authors carried out the literature search using two databases independently, including PubMed, and Web of Science. The review included prospective and retrospective studies using LITT to treat brain metastases. RESULTS: Twenty-two original articles were analyzed in this review, particularly clinical outcomes and complications. We have also provided our institutional experience in the use of LITT to treat brain metastases and addressed future perspectives for the use of this technology. CONCLUSIONS: The current literature supports LITT as a safe and effective therapy for patients with brain metastases that have failed SRS. Larger studies are still required to better evaluate the use of systemic therapy in concomitance with LITT. New images modalities may enable optimized treatment and outcomes.

Laser Interstitial Thermal Therapy in the treatment of brain metastases and radiation necrosis.

Stereotactic Radiosurgery has become the main treatment for patients with limited number of brain metastases (BM). Recently, with the increasing use of this modality, there is a growth in recurrence cases. Recurrence after radiation therapy can be divided in changes favoring either tumor recurrence or radiation necrosis (RN). Laser Interstitial Thermal Therapy (LITT) is minimally invasive treatment modality that has been used to treat primary and metastatic brain tumors. When associated with real-time thermometry using Magnetic Resonance Imaging, the extent of ablation can be controlled to provide maximum coverage and avoid eloquent areas. The objective of this study was to investigate the use of LITT in the treatment of BM. An extensive review of the relevant literature was conducted and the outcome results are discussed. There is an emphasis on safety and local control rate of patients treated with this modality. The findings of our study suggest that LITT is a viable safe technique to treat recurrent BM, especially in patients with deep-seated lesions where surgical resection is not an option.

Immunotherapy response evaluation with magnetic resonance elastography (MRE) in advanced HCC.

BACKGROUND: Currently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC. MATERIALS AND METHODS: This was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6 weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and number of intratumoral CD3+ T lymphocytes. Analysis was performed using descriptive statistics and Spearman correlation (R); p-value < 0.05 was considered statistically significant. RESULTS: Nine patients were evaluable. Median age was 71 years (range, 54-78). Etiology of liver disease was HCV (n = 4), HBV (n = 1) and NASH (n = 4). Median OS and TTP were 44 weeks and 13 weeks, respectively. Average baseline HCC stiffness and change in HCC stiffness were 5.0 kPa and 0.12 kPa, respectively. In contrast, average non-tumor liver stiffness was 3.2 kPa, and did not significantly change at 6 weeks (p = 0.42). Average size of measured tumor and change in size were 4 cm and - 0.32 cm, respectively. Change in HCC stiffness at 6 weeks correlated significantly with OS (R = 0.81), and TTP (R = 0.88,p < 0.01). Abundance of intratumoral T lymphocytes on tumor biopsy correlated significantly with HCC stiffness (R = 0.79,p = 0.007). CONCLUSION: Our pilot MRE data suggests early change in tumor stiffness may be an indicator of immunotherapy response in patients with advanced HCC.

Dynamin impacts homology-directed repair and breast cancer response to chemotherapy.

After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapy-resistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy.

Rare-Earth-Doped Nanoparticles for Short-Wave Infrared Fluorescence Bioimaging and Molecular Targeting of αVß3-Expressing Tumors.

The use of short-wave infrared (SWIR) light for fluorescence bioimaging offers the advantage of reduced photon scattering and improved tissue penetration compared to traditional shorter wavelength imaging approaches. While several nanomaterials have been shown capable of generating SWIR emissions, rare-earth-doped nanoparticles (REs) have emerged as an exceptionally bright and biocompatible class of SWIR emitters. Here, we demonstrate SWIR imaging of REs for several applications, including lymphatic mapping, real-time monitoring of probe biodistribution, and molecular targeting of the αvß3 integrin in a tumor model. We further quantified the resolution and depth penetration limits of SWIR light emitted by REs in a customized imaging unit engineered for SWIR imaging of live small animals. Our results indicate that SWIR light has broad utility for preclinical biomedical imaging and demonstrates the potential for molecular imaging using targeted REs.

MRI-Guided Interventions in Musculoskeletal System.

Image-guided interventions in the musculoskeletal system require accurate detection and characterization of lesions involving bone and soft tissues. Magnetic resonance imaging (MRI) has superior soft tissue contrast resolution particularly in bone and soft tissues where computed tomography and ultrasonography have significant limitations. In addition, the multiplanar imaging capabilities of MRI facilitate targeting lesions and tracking interventional devices. Although conventional diagnostic MRI sequences suffer from motion sensitivity and prolonged imaging time, recently developed fast imaging sequences allow for rapid acquisition of high-quality images, rendering MRI more suitable for image-guided interventions. Although computed tomography and ultrasonography still dominate the spectrum of image-guided interventions in the musculoskeletal system, many MRI-guided procedures have been developed and are well established in routine clinical work. In addition, new techniques and novel MRI-guided applications are being developed to address complex clinical problems in a minimally invasive fashion.

A heterogeneous tissue model for treatment planning for magnetic resonance-guided laser interstitial thermal therapy.

We evaluated a physics-based model for planning for magnetic resonance-guided laser interstitial thermal therapy for focal brain lesions. Linear superposition of analytical point source solutions to the steady-state Pennes bioheat transfer equation simulates laser-induced heating in brain tissue. The line integral of the photon attenuation from the laser source enables computation of the laser interaction with heterogeneous tissue. Magnetic resonance thermometry data sets (n = 31) were used to calibrate and retrospectively validate the model's thermal ablation prediction accuracy, which was quantified by the Dice similarity coefficient (DSC) between model-predicted and measured ablation regions (T > 57 °C). A Gaussian mixture model was used to identify independent tissue labels on pre-treatment anatomical magnetic resonance images. The tissue-dependent optical attenuation coefficients within these labels were calibrated using an interior point method that maximises DSC agreement with thermometry. The distribution of calibrated tissue properties formed a population model for our patient cohort. Model prediction accuracy was cross-validated using the population mean of the calibrated tissue properties. A homogeneous tissue model was used as a reference control. The median DSC values in cross-validation were 0.829 for the homogeneous model and 0.840 for the heterogeneous model. In cross-validation, the heterogeneous model produced a DSC higher than that produced by the homogeneous model in 23 of the 31 brain lesion ablations. Results of a paired, two-tailed Wilcoxon signed-rank test indicated that the performance improvement of the heterogeneous model over that of the homogeneous model was statistically significant (p < 0.01).

Holographic aperture ladar with range compression.

Simultaneous range compression and aperture synthesis is experimentally demonstrated with a stepped linear frequency modulated waveform and holographic aperture ladar. The resultant three-dimensional (3D) data has high resolution in the aperture synthesis dimension and is recorded using a conventional low bandwidth focal plane array. Individual cross-range field segments are coherently combined using data driven registration and phase correction methods allowing range compression to be performed without the benefit of a coherent waveform. Furthermore, we demonstrate a synergistically enhanced ability to discriminate image objects due to the coaction of range compression and aperture synthesis. We show that two objects can be precisely located in 3D space, despite being unresolved in two directions, due to resolution gains in both the range and azimuth cross-range dimensions.

SDF-1 Blockade Enhances Anti-VEGF Therapy of Glioblastoma and Can Be Monitored by MRI.

Despite the approval of antiangiogenic therapy for glioblastoma multiforme (GBM) patients, survival benefits are still limited. One of the resistance mechanisms for antiangiogenic therapy is the induction of hypoxia and subsequent recruitment of macrophages by stromal-derived factor (SDF)-1α (CXCL-12). In this study, we tested whether olaptesed pegol (OLA-PEG, NOX-A12), a novel SDF-1α inhibitor, could reverse the recruitment of macrophages and potentiate the antitumor effect of anti-vascular endothelial growth factor (VEGF) therapy. We also tested whether magnetic resonance imaging (MRI) with ferumoxytol as a contrast agent could provide early information on macrophage blockade. Orthotopic human G12 glioblastomas in nude mice and rat C6 glioblastomas were employed as the animal models. These were treated with bevacizumab or B-20, both anti-VEGF antibodies. Rats were MR imaged with ferumoxytol for macrophage detection. Tumor hypoxia and SDF-1α expression were elevated by VEGF blockade. Adding OLA-PEG to bevacizumab or B-20 significantly prolonged the survival of rodents bearing intracranial GBM compared with anti-VEGF therapy alone. Intratumoral CD68+ tumor associated macrophages (TAMs) were increased by VEGF blockade, but the combination of OLA-PEG + VEGF blockade markedly lowered TAM levels compared with VEGF blockade alone. MRI with ferumoxytol as a contrast agent noninvasively demonstrated macrophage reduction in OLA-PEG + anti-VEGF-treated rats compared with VEGF blockade alone. In conclusion, inhibition of SDF-1 with OLA-PEG inhibited the recruitment of TAMs by VEGF blockage and potentiated its antitumor efficacy in GBM. Noninvasive MRI with ferumoxytol as a contrast agent provides early information on the effect of OLA-PEG in reducing TAMs.

Phase gradient algorithm method for three-dimensional holographic ladar imaging.

Three-dimensional (3D) holographic ladar uses digital holography with frequency diversity to add the ability to resolve targets in range. A key challenge is that since individual frequency samples are not recorded simultaneously, differential phase aberrations may exist between them, making it difficult to achieve range compression. We describe steps specific to this modality so that phase gradient algorithms (PGA) can be applied to 3D holographic ladar data for phase corrections across multiple temporal frequency samples. Substantial improvement of range compression is demonstrated with a laboratory experiment where our modified PGA technique is applied. Additionally, the PGA estimator is demonstrated to be efficient for this application, and the maximum entropy saturation behavior of the estimator is analytically described.

Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization.

BACKGROUND: Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell-derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. METHODS: To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. RESULTS: GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. CONCLUSION: CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy.

Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts.

Bavituximab is a chimeric monoclonal antibody with immune modulating and tumor-associated vascular disrupting properties demonstrated in models of non-small cell lung cancer (NSCLC). The molecular target of Bavituximab, phosphatidylserine (PS), is exposed on the outer leaflet of the membrane bi-layer of malignant vascular endothelial cells and tumor cells to a greater extent than on normal tissues. We evaluated the tumor-targeting properties of Bavituximab for imaging of NSCLC xenografts when radiolabeled with (111)In through conjugation with a bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). In vitro binding of (111)In-DOTA-Bavituximab to PS was determined by enzyme-linked immunosorbent assay (ELISA). Biodistribution of (111)In-DOTA-Bavituximab was conducted in normal rats, which provided data for dosimetry calculation. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed in athymic nude rats bearing A549 NSCLC xenografts. At the molar conjugation ratio of 0.54 DOTA per Bavituximab, the PS binding affinity of (111)In-DOTA-Bavituximab was comparable to that of unmodified Bavituximab. Based on the quantitative SPECT/CT imaging data analysis, (111)In-DOTA-Bavituximab demonstrated tumor-specific uptake as measured by the tumor-tomuscle ratio, which peaked at 5.2 at 72 hr post-injection. In contrast, the control antibody only presented a contrast of 1.2 at the same time point.These findings may underlie the diagnostic efficacy and relative low rates of systemic vascular and immune-related toxicities of this immunoconjugate. Future applications of (111)In-DOTA-bavituximab may include prediction of efficacy, indication of tumor immunologic status, or characterization of radiographic findings.

Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular Imaging.

Beta-emitting isotopes Fluorine-18 and Yttrium-90 are tested for their potential to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs). AuNCs excited by either medical radioisotope are found to be highly effective ionizing radiation energy transfer mediators, suitable for in vivo optical imaging. AuNCs synthesized with protein templates convert beta-decaying radioisotope energy into tissue-penetrating optical signals between 620 and 800 nm. Optical signals are not detected from AuNCs incubated with Technetium-99m, a pure gamma emitter that is used as a control. Optical emission from AuNCs is not proportional to Cerenkov radiation, indicating that the energy transfer between the radionuclide and AuNC is only partially mediated by Cerenkov photons. A direct Coulombic interaction is proposed as a novel and significant mechanism of energy transfer between decaying radionuclides and AuNCs.

Phosphatidylserine-targeted molecular imaging of tumor vasculature by magnetic resonance imaging.

Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable endothelial cells in tumor vasculature, but not in normal blood vessels. In the present study, we report the use of PGN635, a novel human monoclonal antibody that specifically targets PS, for in vivo molecular MRI of tumor vasculature. The F(ab')2 fragments of PGN635 were conjugated to polyethylene glycol (PEG) coated iron oxide nanoparticles (IO). Targeting specificity of the PS-targeted Nanoprobe, IO-PGN635F(ab')2 was first confirmed by in vitro MRI and histological staining. In vivo longitudinal MRI was then performed before and after i.v. injection of IO-PGN635F(ab')2 into mice bearing 4T1 breast tumors. T2-weighted MR images at 9.4 T revealed inhomogeneous signal loss in tumor as early as 2 h post injection. Furthermore, ionizing radiation induced a significant increase in PS exposure on tumor vascular endothelial cells, resulting in significantly enhanced and sustained tumor contrast (p < 0.05). Spatially heterogeneous MRI contrast correlated well with histological staining of tumor vascular endothelium. Our studies suggest that PS exposed within the lumen of tumor vasculature is a highly specific and useful biomarker for targeted MRI contrast agents.