Two-site microendoscopic imaging probe for simultaneous three-dimensional imaging at two anatomic locations in tissues.

Systems that can image in three dimensions at cellular resolution and across different locations within an organism may enable insights into complex biological processes, such as immune responses, for which a single location measurement may be insufficient. In this Letter, we describe an in vivo two-site imaging probe (TIP) that can simultaneously image two anatomic sites with a maximum separation of a few centimeters. The TIP consists of two identical bendable graded index (GRIN) lenses and is demonstrated by a two-photon two-color fluorescence imaging system. Each GRIN lens has a field of view of 162 × 162 × 170 µm3, a nominal numerical aperture of 0.5, a magnification of 0.7, and working distances of 0.2 mm in air for both ends. A blind linear unmixing algorithm is applied to suppress bleedthrough between channels. We use this system to successfully demonstrate two-site two-photon two-color imaging of two biomedically relevant samples, i.e., (1) a mixture of two autofluorescent anti-cancer drugs and (2) a live hybrid tumor consisting of two spectrally distinct fluorescent cell lines.

PET/CT-Guided Tumor Ablation, From the AJR "How We Do It" Special Series.

PET/CT guidance during percutaneous tumor ablation procedures combines metabolic and anatomic imaging, providing a powerful approach that can improve intraprocedural tumor visibility and ablation margin evaluation for a variety of cancers. This article reviews key advantages of the use of PET/CT as guidance for tumor ablation and describes the authors' technique for performing such procedures, highlighting the application of PET/CT for each procedural stage, including planning, targeting, monitoring, and assessment of results. Practical considerations in establishing and operating an interventional PET/CT practice are discussed. Suggestions for overcoming logistical challenges that have historically limited procedural PET/CT adoption are proposed. Several emerging procedural approaches relating to PET/CT and other molecular or anatomic imaging technologies are briefly explored.

Reliability and Management Outcomes Following a Percutaneous Biopsy Diagnosis of Oncocytoma: A 15-year Retrospective Analysis.

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma (n = 107), likely oncocytoma (n = 12), oncocytic neoplasm (n = 28), and indeterminate with oncocytoma in differential (n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories (P = .37) or initial (P = .84) or final management strategies (P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

Image-Guided Ablation of Recurrent or Unresectable Intrahepatic Cholangiocarcinoma.

PURPOSE: To assess the safety and effectiveness of image-guided ablation of recurrent or unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: In this retrospective study, 25 patients (14 women; age, 36-84 years) underwent 37 image-guided liver tumor ablation procedures to treat 47 ICCs (May 2004 to January 2022). At initial diagnosis, 20 patients had Stage 1 or 2 disease and 5 had Stage 3 or 4 disease. Before ablation, 19 (76.0%) of the 25 patients had progressed through prior treatments, including resection (n = 11), chemotherapy (n = 11), transarterial embolization (n = 3), or radiotherapy (n = 1); 6 (24.0%) of the 25 patients were treatment naïve. Ablation modality selection was based on patient and tumor characteristics and operator preference. Primary outcomes included local progression-free survival (LPFS) and overall survival (OS) after ablation. Statistical analysis included Kaplan-Meier (KM) survival analyses and Cox proportional hazards models. RESULTS: The mean ablated tumor size was 2.0 cm ± 1.2 (range, 0.5-5.0 cm). The 1-, 2-, and 5-year LPFS rates were 84.0% (95% CI, 72.9-96.8), 73.0% (95% CI, 59.0-90.4), and 59.5% (95% CI, 41.6-85.1), respectively. The 1-, 2-, and 5-year secondary LPFS rates were 89.5% (95% CI, 80.2-99.9), 81.9% (95% CI, 69.4-96.6), and 75.6% (95% CI, 60.2-94.9). The 1-, 2-, and 5-year LPFS rates for tumors ≤2 cm in size were all 95.8% (95% CI, 88.2-100.0). The 1-, 2-, and 5-year OS rates were 78.5% (95% CI, 63.5-97.2), 68.4% (95% CI, 51.3-91.1), and 43.5% (95% CI, 23.5-80.5). Larger tumor size was associated with decreased time to local progression (hazard ratio, 1.93; P = .012). CONCLUSIONS: Percutaneous ablation provided favorable intermediate to long-term disease control for patients with recurrent or inoperable cholangiocarcinoma.

PET/CT Fluoroscopy during PET/CT-Guided Interventions: Initial Experience.

This study assessed the feasibility and functionality of the use of a high-speed image fusion technology to generate and display positron emission tomography (PET)/computed tomography (CT) fluoroscopic images during PET/CT-guided tumor ablation procedures. Thirteen patients underwent 14 PET/CT-guided ablations for the treatment of 20 tumors. A Food and Drug Administration-cleared multimodal image fusion platform received images pushed from a scanner, followed by near-real-time, nonrigid image registration. The most recent intraprocedural PET dataset was fused to each single-rotation CT fluoroscopy dataset as it arrived, and the fused images were displayed on an in-room monitor. PET/CT fluoroscopic images were generated and displayed in all procedures and enabled more confident targeting in 3 procedures. The mean lag time from CT fluoroscopic image acquisition to the in-room display of the fused PET/CT fluoroscopic image was 21 seconds ± 8. The registration accuracy was visually satisfactory in 13 of 14 procedures. In conclusion, PET/CT fluoroscopy was feasible and may have the potential to facilitate PET/CT-guided procedures.

Tumor and Ablation Margin Visibility during Cryoablation of Musculoskeletal Tumors: Comparing Intraprocedural PET/CT Images with CT-Only Images.

PURPOSE: To compare tumor and ice-ball margin visibility on intraprocedural positron emission tomography (PET)/computed tomography (CT) and CT-only images and report technical success, local tumor progression, and adverse event rates for PET/CT-guided cryoablation procedures for musculoskeletal tumors. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPAA)-compliant and institutional review board-approved retrospective study evaluated 20 PET/CT-guided cryoablation procedures performed with palliative and/or curative intent to treat 15 musculoskeletal tumors in 15 patients from 2012 to 2021. Cryoablation was performed using general anesthesia and PET/CT guidance. Procedural images were reviewed to determine the following: (a) whether the tumor borders could be fully assessed on PET/CT or CT-only images; and (b) whether tumor ice-ball margins could be fully assessed on PET/CT or CT-only images. The ability to visualize tumor borders and ice-ball margins on PET/CT images was compared with that on CT-only images. RESULTS: Tumor borders were fully assessable for 100% (20 of 20; 95% CI, 0.83-1) of procedures on PET/CT versus 20% (4 of 20; 95 CI, 0.057-0.44) of procedures on CT only (P < .001). The tumor ice-ball margin was fully assessable in 80% (16 of 20; 95% CI, 0.56-0.94) of procedures using PET/CT versus 5% (1 of 20; 95% CI, 0.0013-0.25) of procedures using CT only (P < .001). Primary technical success was achieved in 75% (15 of 20; 95% CI, 0.51-0.91) of procedures. There was local tumor progression in 23% (3/13; 95% CI, 0.050-0.54) of the treated tumors with at least 6 months of follow-up. There were 3 adverse events (1 Grade 3, 1 Grade 2, and 1 Grade 1). CONCLUSIONS: PET/CT-guided cryoablation of musculoskeletal tumors can provide superior intraprocedural visualization of the tumor and ice-ball margins compared with that provided by CT alone. Further studies are warranted to confirm the long-term efficacy and safety of this approach.

Bendable long graded index lens microendoscopy.

Graded index (GRIN) lens endoscopy has broadly benefited biomedical microscopic imaging by enabling accessibility to sites not reachable by traditional benchtop microscopes. It is a long-held notion that GRIN lenses can only be used as rigid probes, which may limit their potential for certain applications. Here, we describe bendable and long-range GRIN microimaging probes for a variety of potential micro-endoscopic biomedical applications. Using a two-photon fluorescence imaging system, we have experimentally demonstrated the feasibility of three-dimensional imaging through a 500-µm-diameter and ∼11 cm long GRIN lens subject to a cantilever beam-like deflection with a minimum bend radius of ∼25 cm. Bend-induced perturbation to the field of view and resolution has also been investigated quantitatively. Our development alters the conventional notion of GRIN lenses and enables a range of innovative applications. For example, the demonstrated flexibility is highly desirable for implementation into current and emerging minimally invasive clinical procedures, including a pioneering microdevice for high-throughput cancer drug selection.

Positron Emission Tomography and Computed Tomography Contributions to Patient Dose and Personnel Exposure to Radiation during PET/CT-Guided Tumor Ablations.

This study sought to quantify the positron emission tomography (PET) and computed tomography (CT) components of patient radiation doses and personnel exposure to radiations during PET/CT-guided tumor ablations and assess the utility of a rolling lead shield for operator protection. Two operators performed 21 PET/CT-guided ablations behind a customized, 25-mm-thick lead shield with midchest-to-midthigh coverage. The mean patient radiation dose per procedure was 3.90 mSv ± 1.13 (11.3%) from PET and 30.51 mSv ± 19.05 (88.7%) from CT. The mean primary and secondary operator exposure outside neck-level thyroid shields was 0.05 and 0.02 mSv per procedure, respectively. The radiation exposure levels behind the rolling lead shield, inside the primary operator's thyroid shield, and on the other personnel were below the measurable threshold cumulatively over 21 procedures. The mean PET exposure level at continuous close proximity to patients was 0.02 mSv per procedure. The PET radiation doses to the patients and personnel were small. Thus, the rolling lead shield provided limited benefit.

A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues.

Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While the previous system provided a bulk measurement of both drug delivery and tissue response from a given region of the tumor, it was incapable of visualizing drug distribution and tissue responses in a three-dimensional (3D) way, thus missing the critical relationship between drug concentration and effect. Here we demonstrate a next-generation system that couples multiplexed intratumor drug release with continuous 3D spatial imaging of the tumor microenvironment via the integration of a miniaturized two-photon micro-endoscope. This enables optical sectioning within the live tissue microenvironment to effectively profile the entire tumor region adjacent to the microdevice across time. Using this novel microimaging-microdevice (MI-MD) system, we successfully demonstrated the four-dimensional imaging (3 spatial dimensions plus time) of local drug delivery in tissue phantom and tumors. Future studies include the use of the MI-MD system for monitoring of localized intra-tissue drug release and concurrent measurement of tissue responses in live organisms, with applications to study drug resistance due to nonuniform drug distribution in tumors, or immune cell responses to anti-cancer agents.

Percutaneous CT- and MRI-guided Cryoablation of cT1 Renal Cell Carcinoma: Intermediate- to Long-term Outcomes in 307 Patients.

Background Percutaneous ablation for cT1 renal cell carcinoma (RCC) remains underused, partially because of heterogeneous and limited long-term outcomes data assessing recent cryoablation methods. Purpose To report intermediate- to long-term outcomes of image-guided percutaneous cryoablation of cT1 RCC and to compare outcomes for CT versus MRI guidance. Materials and Methods This HIPAA-compliant retrospective single-institution study assessed patients who underwent percutaneous cryoablation for solitary pathology-proven cT1 RCC between August 2000 and July 2017. Tumors (cT1a, n = 282; cT1b, n = 25; size range, 0.6-6.5 cm; median size, 2.5 cm) underwent cryoablation with CT (n = 155) or MRI (n = 152) guidance. Primary end points of overall survival (OS), disease-specific survival (DSS), imaging-confirmed disease-free survival (DFS), and local progression-free survival (LPFS) were calculated by using Kaplan-Meier analysis. Secondary end points of technique efficacy and adverse event rate were also calculated. Primary and secondary end points for CT and MRI guidance were compared by using univariable regression analysis. Results A total of 307 patients (mean age, 68 years ± 11 [standard deviation]; 192 men) were evaluated. Median clinical follow-up lasted 95 months (range, 8-219 months), and median imaging follow-up lasted 41 months (range, 0-189 months). Survival metrics at 3, 5, 10, and 15 years, respectively, included OS of 91% (95% confidence interval [CI]: 88%, 94%), 86% (95% CI: 82%, 90%), 78% (95% CI: 73%, 84%), and 76% (95% CI: 69%, 83%); DSS of 99.6% (95% CI: 99%, 100%), 99% (95% CI: 98%, 100%), 99% (95% CI: 98%, 100%), and 99% (95% CI: 98%, 100%); DFS of 94% (95% CI: 92%, 97%), 91% (95% CI: 88%, 96%), 88% (95% CI: 83%, 93%), and 88% (95% CI: 83%, 93%); and LPFS of 97% (95% CI: 94%, 99%), 95% (95% CI: 93%, 98%), 95% (95% CI: 93%, 98%), and 95% (95% CI: 93%, 98%). Survival did not significantly differ between CT and MRI guidance, with univariable Cox regression analysis hazard ratios of 0.97 (95% CI: 0.57, 1.67; P = .92) for OS, 0.63 (95% CI: 0.26, 1.52; P = .30) for DFS, and 0.83 (95% CI: 0.26, 2.74; P = .77) for LPFS. Primary and secondary technique efficacy were 96% and 99%, respectively. Overall adverse event rate was 14% (43 of 307), including 11 grade 3 events and three grade 4 events according to the Common Terminology Criteria for Adverse Events. Conclusion Percutaneous CT- and MRI-guided cryoablation of cT1 renal cell carcinoma had similar excellent intermediate- and long-term outcomes. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Liver stiffness assessment with tagged MRI of cardiac-induced liver motion in cirrhosis patients.

PURPOSE: To assess liver stiffness using magnetization-tagged magnetic resonance imaging (MRI) to measure the cardiac-induced motion in the liver of cirrhosis patients with known Child-Pugh scores. MATERIALS AND METHODS: Tagged MRI was performed using a 3T MR scanner on 52 cirrhosis patients classified into two groups: liver cirrhosis with Child-Pugh A (LCA; n = 39) and liver cirrhosis with Child-Pugh B or C (LCBC; n = 13). We also included 19 healthy controls. Tagged images were acquired encompassing both the liver and the heart. The corresponding displacement and strains were calculated using a Gabor filter bank. The maximum displacement (MaxDisp) was found over the cardiac cycle, as well as the local maximum P1 (MaxP1) and minimum P2 strains (MinP2). Group comparisons were made without and with adjustment for age and gender. RESULTS: In control, LCA, and LCBC groups, the MaxDisp was 3.98 ± 0.88 mm, 2.52 ± 0.73 mm, and 1.86 ± 0.77 mm; the MaxP1 was 0.10 ± 0.02, 0.04 ± 0.01, and 0.02 ± 0.01; and the MinP2 was -0.08 ± 0.01, -0.05 ± 0.02, and -0.03 ± 0.01, respectively. Statistically significant differences were found between groups (P < 0.05 for all). CONCLUSION: This method measures cardiac-induced liver motion and deformation to assess liver stiffness. Significant differences were found in our stiffness measures between control, LCA, and LCBC groups, with more severe disease being associated with greater stiffness.

Evaluation of diastolic function by three-dimensional volume tracking of the mitral annulus with cardiovascular magnetic resonance: comparison with tissue Doppler imaging.

BACKGROUND: Measurement of mitral annulus (MA) dynamics is an important component of the evaluation of left ventricular (LV) diastolic function; MA velocities are commonly measured using tissue Doppler imaging (TDI). This study aimed to examine the clinical potential of a semi-automated cardiovascular magnetic resonance (CMR) technique for quantifying global LV diastolic function, using 3D volume tracking of the MA with conventional cine-CMR images. METHODS: 124 consecutive patients with normal ejection fraction underwent both clinically indicated transthoracic echocardiography (TTE) and CMR within 2 months. Interpolated 3D reconstruction of the MA over time was performed with semi-automated atrioventricular junction (AVJ) tracking in long-axis cine-CMR images, producing an MA sweep volume over the cardiac cycle. CMR-based diastolic function was evaluated, using the following parameters: peak volume sweep rates in early diastole (PSRE) and atrial systole (PSRA), PSRE/PSRA ratio, deceleration time of sweep volume (DTSV), and 50% diastolic sweep volume recovery time (DSVRT50); these were compared with TTE diastolic measurements. RESULTS: Patients with TTE-based diastolic dysfunction (n = 62) showed significantly different normalized MA sweep volume profiles compared to those with TTE-based normal diastolic function (n = 62), including a lower PSRE (5.25 ± 1.38 s-1 vs. 7.72 ± 1.7 s-1), a higher PSRA (6.56 ± 1.99 s-1 vs. 4.67 ± 1.38 s-1), a lower PSRE/PSRA ratio (0.9 ± 0.44 vs. 1.82 ± 0.69), a longer DTSV (144 ± 55 ms vs. 96 ± 37 ms), and a longer DSVRT50 (25.0 ± 11.0% vs. 15.6 ± 4.0%) (all p < 0.05). CMR diastolic parameters were independent predictors of TTE-based diastolic dysfunction after adjusting for left ventricular hypertrophy, hypertension, and coronary artery disease. Good correlations were observed between CMR PSRE/PSRA and early-to-late diastolic annular velocity ratios (e'/a') measured by TDI (r = 0.756 to 0.828, p < 0.001). CONCLUSIONS: 3D MA sweep volumes generated by semi-automated AVJ tracking in routinely acquired CMR images yielded diastolic parameters that were effective in identifying patients with diastolic dysfunction when correlated with TTE-based variables.

A novel and practical cardiovascular magnetic resonance method to quantify mitral annular excursion and recoil applied to hypertrophic cardiomyopathy.

BACKGROUND: We have developed a novel and practical cardiovascular magnetic resonance (CMR) technique to evaluate left ventricular (LV) mitral annular motion by tracking the atrioventricular junction (AVJ). To test AVJ motion analysis as a metric for LV function, we compared AVJ motion variables between patients with hypertrophic cardiomyopathy (HCM), a group with recognized systolic and diastolic dysfunction, and healthy volunteers. METHODS: We retrospectively evaluated 24 HCM patients with normal ejection fractions (EF) and 14 healthy volunteers. Using the 4-chamber view cine images, we tracked the longitudinal motion of the lateral and septal AVJ at 25 time points during the cardiac cycle. Based on AVJ displacement versus time, we calculated maximum AVJ displacement (MD) and velocity in early diastole (MVED), velocity in diastasis (VDS) and the composite index VDS/MVED. RESULTS: Patients with HCM showed significantly slower median lateral and septal AVJ recoil velocities during early diastole, but faster velocities in diastasis. We observed a 16-fold difference in VDS/MVED at the lateral AVJ [median 0.141, interquartile range (IQR) 0.073, 0.166 versus 0.009 IQR -0.006, 0.037, P < 0.001]. Patients with HCM also demonstrated significantly less mitral annular excursion at both the septal and lateral AVJ. Performed offline, AVJ motion analysis took approximately 10 minutes per subject. CONCLUSIONS: Atrioventricular junction motion analysis provides a practical and novel CMR method to assess mitral annular motion. In this proof of concept study we found highly statistically significant differences in mitral annular excursion and recoil between HCM patients and healthy volunteers.

Lung Needle Biopsy and Lung Ablation: Indications, Patient Management, and Postprocedure Imaging Findings.

The clinical role and use of percutaneous transthoracic needle biopsy (TTNB) and ablation of lung tumors are evolving. Here we discuss important considerations for referring providers, including current and emerging indications supported by guidelines, critical aspects of pre and postprocedure patient management, and expected postprocedure imaging findings.

Image-guided percutaneous ablation of hepatic epithelioid hemangioendothelioma.

PURPOSE: Disease control and survival following percutaneous ablation of hepatic epithelioid hemangioendothelioma (EHE) was studied retrospectively. METHODS: Six patients underwent 16 image-guided ablation procedures to treat 35 liver tumors from 2015 to 2022 (17 microwave ablation, 9 irreversible electroporation, 8 cryoablation, and 1 radiofrequency ablation). Technical success, local progression, intrahepatic progression, distant progression, overall survival, and adverse events were assessed. RESULTS: Four of six (67%) patients were treatment naïve prior to ablation. The mean length of imaging follow-up from first ablation procedure was 43.0 ± 31.2 months. Thirty-three of 35 (94.3%) ablated tumors did not progress locally. Three of 6 patients (50%) had new intrahepatic progression and underwent repeat ablation or systemic treatment. No extrahepatic progression was observed. One patient died from EHE 2.7 years after initial diagnosis. No severe adverse events occurred. CONCLUSION: Percutaneous ablation is feasible, often in a staged fashion, and may provide favorable intermediate to long-term disease control for patients with hepatic EHE.

Superparamagnetic iron oxide nanoparticle enhanced percutaneous microwave ablation: Ex-vivo characterization using magnetic resonance thermometry.

BACKGROUND: Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal tissue heating. It can treat cancer and other diseases with lower morbidity than conventional surgery, but one major limitation is the lack of control over the heating region around the ablation needle. Superparamagnetic iron oxide nanoparticles have the potential to enhance and control pMWA heating due to their ability to absorb microwave energy and their ease of local delivery. PURPOSE: The purpose of this study is to experimentally quantify the capabilities of FDA-approved superparamagnetic iron oxide Feraheme nanoparticles (FHNPs) to enhance and control pMWA heating. This study aims to determine the effectiveness of locally injected FHNPs in increasing the maximum temperature during pMWA and to investigate the ability of FHNPs to create a controlled ablation zone around the pMWA needle. METHODS: PMWA was performed using a clinical ablation system at 915 MHz in ex-vivo porcine liver tissues. Prior to ablation, 50 uL 5 mg/mL FHNP injections were made on one side of the pMWA needle via a 23-gauge needle. Local temperatures at the FHNP injection site were directly compared to equidistant control sites without FHNP. First, temperatures were compared using directly inserted thermocouples. Next, temperatures were measured non-invasively using magnetic resonance thermometry (MRT), which enabled comprehensive four-dimensional (volumetric and temporal) assessment of heating effects relative to nanoparticle distribution, which was quantified using dual-echo ultrashort echo time (UTE) subtraction MR imaging. Maximum heating within FHNP-exposed tissues versus control tissues were compared at multiple pMWA energy delivery settings. The ability to generate a controlled asymmetric ablation zone using multiple FHNP injections was also tested. Finally, intra-procedural MRT-derived heat maps were correlated with gold standard gross pathology using Dice similarity analysis. RESULTS: Maximum temperatures at the FHNP injection site were significantly higher than control (without FHNP) sites when measured using direct thermocouples (93.1 ± 6.0°C vs. 57.2 ± 8.1°C, p = 0.002) and using non-invasive MRT (115.6 ± 13.4°C vs. 49.0 ± 10.6°C, p = 0.02). Temperature difference between FHNP-exposed and control sites correlated with total energy deposition: 66.6 ± 17.6°C, 58.1 ± 8.5°C, and 20.8 ± 9.2°C at high (17.5 ± 2.2 kJ), medium (13.6 ± 1.8 kJ), and low (8.8 ± 1.1 kJ) energies, respectively (all pairwise p < 0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9 ± 0.2 cm radially of the injection site and a local lethal heating zone confined to within 1.1 ± 0.4 cm radially of the injection epicenter. Multiple injections enabled a controllable, asymmetric ablation zone to be generated around the ablation needle, with maximal ablation radius on the FHNP injection side of 1.6 ± 0.2 cm compared to 0.7 ± 0.2 cm on the non-FHNP side (p = 0.02). MRT intra-procedural predicted ablation zone correlated strongly with post procedure gold-standard gross pathology assessment (Dice similarity 0.9). CONCLUSIONS: Locally injected FHNPs significantly enhanced pMWA heating in liver tissues, and were able to control the ablation zone shape around a pMWA needle. MRI and MRT allowed volumetric real-time visualization of both FHNP distribution and FHNP-enhanced pMWA heating that was useful for intra-procedural monitoring. This work strongly supports further development of a FHNP-enhanced pMWA paradigm; as all individual components of this approach are approved for patient use, there is low barrier for clinical translation.

Feasibility and safety of bipolar radiofrequency track cautery during percutaneous image-guided abdominal biopsy procedures.

PURPOSE: The purpose of this study was to assess the feasibility and safety of using a bipolar radiofrequency track cautery device during percutaneous image-guided abdominal biopsy procedures in at-risk patients. METHODS: Forty-two patients (26-79 years old; female 44%) with at least one bleeding risk factor who underwent an abdominal image-guided (CT or US) biopsy and intended bipolar radiofrequency track cautery (BRTC) were retrospectively studied. An 18G radiofrequency electrode was inserted through a 17G biopsy introducer needle immediately following coaxial 18G core biopsy, to cauterize the biopsy track using temperature control. Bleeding risk factors, technical success, and adverse events were recorded. RESULTS: BRTC was technically successful in 41/42 (98%) of procedures; in one patient, the introducer needle retracted from the liver due to respiratory motion prior to BRTC. BRTC following percutaneous biopsy was applied during 41 abdominal biopsy procedures (renal mass = 12, renal parenchyma = 10, liver mass = 9, liver parenchyma = 5, splenic mass or parenchyma = 4, gastrohepatic mass = 1). All patients had one or more of the following risk factors: high-risk organ (spleen or renal parenchyma), hypervascular mass, elevated prothrombin time, renal insufficiency, thrombocytopenia, recent anticoagulation or anticoagulation not withheld for recommended interval, cirrhosis, intraprocedural hypertension, brisk back bleeding observed from the introducer needle, or subcapsular tumor location. No severe adverse events (grade 3 or higher) occurred. Two (2/41, 5%) mild (grade 1) bleeding events did not cause symptoms or require intervention. CONCLUSION: Bipolar radiofrequency track cautery was feasible and safe during percutaneous image-guided abdominal biopsy procedures. IRB approval: MBG 2022P002277.

Enhanced Tumor Accumulation of Multimodal Magneto-Plasmonic Nanoparticles via an Implanted Micromagnet-Assisted Delivery Strategy.

One of the major shortcomings of nano carriers-assisted cancer therapeutic strategies continues to be the inadequate tumor penetration and retention of systemically administered nanoformulations and its off-target toxicity. Stromal parameters-related heterogeneity in enhanced permeability and retention effect and physicochemical properties of the nanoformulations immensely contributes to their poor tumor extravasation. Herein, a novel tumor targeting strategy, where an intratumorally implanted micromagnet can significantly enhance accumulation of magneto-plasmonic nanoparticles (NPs) at the micromagnet-implanted tumor in bilateral colorectal tumor models while limiting their off-target accumulation, is demonstrated. To this end, novel multimodal gold/iron oxide NPs comprised of an array of multifunctional moieties with high therapeutic, sensing, and imaging potential are developed. It is also discovered that cancer cell targeted NPs in combination with static magnetic field can selectively induce cancer cell death. A multimodal caspase-3 nanosensor is also developed for real-time visualization of selective induction of apoptosis in cancer cells. In addition, the photothermal killing capability of these NPs in vitro is evaluated, and their potential for enhanced photothermal ablation in tissue samples is demonstrated. Building on current uses of implantable devices for therapeutic purposes, this study envisions the proposed micromagnet-assisted NPs delivery approach may be used to accelerate the clinical translation of various nanoformulations.

Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.

The Translational and Regulatory Development of an Implantable Microdevice for Multiple Drug Sensitivity Measurements in Cancer Patients.

OBJECTIVE: The purpose of this article is to report the translational process of an implantable microdevice platform with an emphasis on the technical and engineering adaptations for patient use, regulatory advances, and successful integration into clinical workflow. METHODS: We developed design adaptations for implantation and retrieval, established ongoing monitoring and testing, and facilitated regulatory advances that enabled the administration and examination of a large set of cancer therapies simultaneously in individual patients. RESULTS: Six applications for oncology studies have successfully proceeded to patient trials, with future applications in progress. CONCLUSION: First-in-human translation required engineering design changes to enable implantation and retrieval that fit with existing clinical workflows, a regulatory strategy that enabled both delivery and response measurement of up to 20 agents in a single patient, and establishment of novel testing and quality control processes for a drug/device combination product without clear precedents. SIGNIFICANCE: This manuscript provides a real-world account and roadmap on how to advance from animal proof-of-concept into the clinic, confronting the question of how to use research to benefit patients.