Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

In vivo Imaging and Pharmacokinetics of Percutaneously Injected Ultrasound and X-ray Imageable Thermosensitive Hydrogel loaded with Doxorubicin versus Free Drug in Swine.

Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region. Secondly, pharmacokinetics of POL loaded with doxorubicin (POLDOX) were evaluated and compared to free doxorubicin injection (DOXSoln) with a Single End Hole Needle. Utilizing 2D and 3D morphometrics from US and x-ray imaging techniques such as Computed Tomography (CT) and Cone Beam CT (CBCT), we monitored the localization and leakage of POLDOX over time. Relative iodine concentrations measured with CBCT following incorporation of an iodinated contrast agent in POL indicated potential drug diffusion and advection transport. Furthermore, US imaging revealed temporal changes, suggesting variations in acoustic intensity, heterogeneity, and echotextures. Notably, 3D reconstruction of the distribution of POL and POLDOX from 2D ultrasound frames was achieved and morphometric data obtained. Pharmacokinetic analysis revealed lower systemic exposure of the drug in various organs with POLDOX formulation compared to DOXSoln formulation. This was demonstrated by a lower area under the curve (852.1 ± 409.1 ng/mL·h vs 2283.4 ± 377.2 ng/mL·h) in the plasma profile, suggesting a potential reduction in systemic toxicity. Overall, the use of POL formulation offers a promising strategy for precise and localized drug delivery, that may minimize adverse effects. Dual modality POL imaging enabled analysis of patterns of gel distribution and morphology, alongside of pharmacokinetics of local delivery. Incorporating hydrogels into drug delivery systems holds significant promise for improving the predictability of the delivered drug and enhancing spatial conformability. These advancements can potentially enhance the safety and precision of anticancer therapy.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

X-ray imageable, drug-loaded hydrogel that forms at body temperature for image-guided, needle-based locoregional drug delivery.

Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

X-ray imageable, drug-loaded hydrogel that forms at body temperature for image-guided, needle- based locoregional drug delivery.

Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An x-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

Smartphone Augmented Reality Outperforms Conventional CT Guidance for Composite Ablation Margins in Phantom Models.

PURPOSE: To develop and evaluate a smartphone augmented reality (AR) system for a large 50-mm liver tumor ablation with treatment planning for composite overlapping ablation zones. MATERIALS AND METHODS: A smartphone AR application was developed to display tumor, probe, projected probe paths, ablated zones, and real-time percentage of the ablated target tumor volume. Fiducial markers were attached to phantoms and an ablation probe hub for tracking. The system was evaluated with tissue-mimicking thermochromic phantoms and gel phantoms. Four interventional radiologists performed 2 trials each of 3 probe insertions per trial using AR guidance versus computed tomography (CT) guidance approaches in 2 gel phantoms. Insertion points and optimal probe paths were predetermined. On Gel Phantom 2, serial ablated zones were saved and continuously displayed after each probe placement/adjustment, enabling feedback and iterative planning. The percentages of tumor ablated for AR guidance versus CT guidance, and with versus without display of recorded ablated zones, were compared among interventional radiologists with pairwise t-tests. RESULTS: The means of percentages of tumor ablated for CT freehand and AR guidance were 36% ± 7 and 47% ± 4 (P = .004), respectively. The mean composite percentages of tumor ablated for AR guidance were 43% ± 1 (without) and 50% ± 2 (with display of ablation zone) (P = .033). There was no strong correlation between AR-guided percentage of ablation and years of experience (r < 0.5), whereas there was a strong correlation between CT-guided percentage of ablation and years of experience (r > 0.9). CONCLUSIONS: A smartphone AR guidance system for dynamic iterative large liver tumor ablation was accurate, performed better than conventional CT guidance, especially for less experienced interventional radiologists, and enhanced more standardized performance across experience levels for ablation of a 50-mm tumor.

Hydrogel drug delivery systems for minimally invasive local immunotherapy of cancer.

Although systemic immunotherapy has achieved durable responses and improved survival for certain patients and cancer types, low response rates and immune system-related systemic toxicities limit its overall impact. Intratumoral (intralesional) delivery of immunotherapy is a promising technique to combat mechanisms of tumor immune suppression within the tumor microenvironment and reduce systemic drug exposure and associated side effects. However, intratumoral injections are prone to variable tumor drug distribution and leakage into surrounding tissues, which can compromise efficacy and contribute to toxicity. Controlled release drug delivery systems such as in situ-forming hydrogels are promising vehicles for addressing these challenges by providing improved spatio-temporal control of locally administered immunotherapies with the goal of promoting systemic tumor-specific immune responses and abscopal effects. In this review we will discuss concepts, applications, and challenges in local delivery of immunotherapy using controlled release drug delivery systems with a focus on intratumorally injected hydrogel-based drug carriers.

Virtual Treatment Zone From Cone Beam CT Commonly Alters Treatment Plan and Identifies Tumor at Risk for Under-Treatment in US or US Fusion-Guided Microwave Ablation of Liver Tumors.

Tumor ablation is included in several major cancer therapy guidelines. One technical challenge of percutaneous ablation is targeting and verification of complete treatment, which is prone to operator variabilities and human imperfections and are directly related to successful outcomes, risk for residual unablated tumor and local progression. The use of "Prediction Ablation Volume Software" may help the operating Interventional Radiologist to better plan, deliver, and verify before the ablation, via virtual treatment zones fused to target tumor. Fused and superimposed images provide 3-dimensional information from different timepoints, just when that information is most useful. The aim of this study is to evaluate the technical success and efficacy of an ablation treatment flowchart provided by a cone beam computed tomography (CBCT) "Prediction Ablation Volume Software." This is a single-center retrospective study. From April 2021 to January 2022, 29 nonconsecutive evaluable patients with 32 lesions underwent liver ablation with Prediction Ablation Volume Software. Each patient was discussed in a multidisciplinary tumor board and underwent an enhanced computed tomography or magnetic resonance imaging approximately 1 month before the procedure, as well as ∼1 month after. Technical success was defined as treatment of the tumor according to the protocol, covered completely by the Prediction Ablation Volume. Technical efficacy was defined as assessment of complete ablation of the target tumor at imaging follow up (∼1 month). Technical success, technical efficacy, and procedural factors were studied. Technical success was achieved in 30 of 32 liver lesions (94%), measuring 20 mm mean maximum diameter. The antenna was repositioned in 16 of 30 (53%) evaluable target lesions. Residual tumor was detected at 1 month imaging follow up in only 4 of 30 (13%) of the treated lesion. Technical efficacy was of 87% in this retrospective description of our process. The implementation of a CBCT Prediction Ablation Volume Software and flowchart for the treatment of liver malignancies altered the procedure, and demonstrated high technical success and efficacy. Such tools are potentially useful for procedural prediction and verification of ablation.

Precision Imaging Guidance in the Era of Precision Oncology: An Update of Imaging Tools for Interventional Procedures.

Interventional oncology (IO) procedures have become extremely popular in interventional radiology (IR) and play an essential role in the diagnosis, treatment, and supportive care of oncologic patients through new and safe procedures. IR procedures can be divided into two main groups: vascular and non-vascular. Vascular approaches are mainly based on embolization and concomitant injection of chemotherapeutics directly into the tumor-feeding vessels. Percutaneous approaches are a type of non-vascular procedures and include percutaneous image-guided biopsies and different ablation techniques with radiofrequency, microwaves, cryoablation, and focused ultrasound. The use of these techniques requires precise imaging pretreatment planning and guidance that can be provided through different imaging techniques: ultrasound, computed tomography, cone-beam computed tomography, and magnetic resonance. These imaging modalities can be used alone or in combination, thanks to fusion imaging, to further improve the confidence of the operators and the efficacy and safety of the procedures. This article aims is to provide an overview of the available IO procedures based on clinical imaging guidance to develop a targeted and optimal approach to cancer patients.

Lifesaving embolization in a massive lumbar artery bleeding: Interventional radiology management.

Vertebral fractures are the most frequent fractures associated with osteoporosis. Thus far, there are no reported cases in literature analyzing intervertebral bleeding as a result of an osteoporotic vertebral fracture. The authors report a case of an 85-year-old woman in hemorrhagic shock for an unusual vertebral fracture causing a massive bleeding, which was contained by the vertebral ligament system inside the body of L4, treated with an endovascular approach. Since there are no guidelines for a treatment for the case mentioned above or similar, our aim is to describe a possible approach to a potentially life-threatening rare event.