Purpose: This paper reports on the design and initial imaging performance of a dedicated conebeam CT (CBCT) system for musculoskeletal (MSK) extremities. The system complements conventional CT and MR and offers a variety of potential clinical and logistical advantages that are likely to be of benefit to diagnosis, treatment planning, and assessment of therapy response in MSK radiology, orthopaedic surgery, and rheumatology. Methods: The scanner design incorporated a host of clinical requirements (e.g., ability to scan the weight-bearing knee in a natural stance) and was guided by theoretical and experimental analysis of image quality and dose. Such criteria identified the following basic scanner components and system configuration: a flat-panel detector (FPD, Varian 3030þ, 0.194 mm pixels); and a low-power, fixed anode x-ray source with 0.5 mm focal spot (SourceRay XRS-125-7K-P, 0.875 kW) mounted on a retractable C-arm allowing for two scanning orientations with the capability for side entry, viz. a standing configuration for imaging of weight-bearing lower extremities and a sitting configuration for imaging of tensioned upper extremity and unloaded lower extremity. Theoretical modeling employed cascaded systems analysis of modulation transfer function (MTF) and detective quantum efficiency (DQE) computed as a function of system geometry, kVp and filtration, dose, source power, etc. Physical experimentation utilized an imaging bench simulating the scanner geometry for verification of theoretical results and investigation of other factors, such as antiscatter grid selection and 3D image quality in phantom and cadaver, including qualitative comparison to conventional CT. Results: Theoretical modeling and benchtop experimentation confirmed the basic suitability of the FPD and x-ray source mentioned above. Clinical requirements combined with analysis of MTF and DQE yielded the following system geometry: a $55 cm source-to-detector distance; 1.3 magnification; a 20 cm diameter bore (20 Â 20 Â 20 cm 3 field of view); total acquisition arc of $240 . The system MTF declines to 50% at $1.3 mm À1 and to 10% at $2.7 mm À1, consistent with submillimeter spatial resolution. Analysis of DQE suggested a nominal technique of 90 kVp (þ0.3 mm Cu added filtration) to provide high imaging performance from $500 projections at less than $0.5 kW power, implying $6.4 mGy (0.064 mSv) for low-dose protocols and $15 mGy (0.15 mSv) for high-quality protocols. The experimental studies show improved image uniformity and contrast-tonoise ratio (without increase in dose) through incorporation of a custom 10:1 GR antiscatter grid. Cadaver images demonstrate exquisite bone detail, visualization of articular morphology, and softtissue visibility comparable to diagnostic CT (10-20 HU contrast resolution). Conclusions:The results indicate that the proposed system will deliver volumetric images of the extremities with soft-tissue contrast resolution comparable to diagnostic CT and improved spatial resolution at potentially reduced dose. Cascaded sys...

Thermal tissue ablation is an interventional procedure increasingly being used for treatment of diverse medical conditions. Microwave ablation is emerging as an attractive modality for thermal therapy of large soft tissue targets in short periods of time, making it particularly suitable for ablation of hepatic and other tumors. Theoretical models of the ablation process are a powerful tool for predicting the temperature profile in tissue and resultant tissue damage created by ablation devices. These models play an important role in the design and optimization of devices for microwave tissue ablation. Furthermore, they are a useful tool for exploring and planning treatment delivery strategies. This review describes the status of theoretical models developed for microwave tissue ablation. It also reviews current challenges, research trends and progress towards development of accurate models for high temperature microwave tissue ablation.

Purpose: This work applies a cascaded systems model for cone-beam CT imaging performance to the design and optimization of a system for musculoskeletal extremity imaging. The model provides a quantitative guide to the selection of system geometry, source and detector components, acquisition techniques, and reconstruction parameters. Methods: The model is based on cascaded systems analysis of the 3D noise-power spectrum (NPS) and noise-equivalent quanta (NEQ) combined with factors of system geometry (magnification, focal spot size, and scatter-to-primary ratio) and anatomical background clutter. The model was extended to task-based analysis of detectability index (d 0 ) for tasks ranging in contrast and frequency content, and d 0 was computed as a function of system magnification, detector pixel size, focal spot size, kVp, dose, electronic noise, voxel size, and reconstruction filter to examine tradeoffs and optima among such factors in multivariate analysis. The model was tested quantitatively versus the measured NPS and qualitatively in cadaver images as a function of kVp, dose, pixel size, and reconstruction filter under conditions corresponding to the proposed scanner. Results: The analysis quantified trade-offs among factors of spatial resolution, noise, and dose. System magnification (M) was a critical design parameter with strong effect on spatial resolution, dose, and x-ray scatter, and a fairly robust optimum was identified at M $ 1.3 for the imaging tasks considered. The results suggested kVp selection in the range of $65-90 kVp, the lower end (65 kVp) maximizing subject contrast and the upper end maximizing NEQ (90 kVp). The analysis quantified fairly intuitive resultse.g., $0.1-0.2 mm pixel size (and a sharp reconstruction filter) optimal for high-frequency tasks (bone detail) compared to $0.4 mm pixel size (and a smooth reconstruction filter) for low-frequency (soft-tissue) tasks. This result suggests a specific protocol for 1 Â 1 (full-resolution) projection data acquisition followed by full-resolution reconstruction with a sharp filter for high-frequency tasks along with 2 Â 2 binning reconstruction with a smooth filter for low-frequency tasks. The analysis guided selection of specific source and detector components implemented on the proposed scanner. The analysis also quantified the potential benefits and points of diminishing return in focal spot size, reduced electronic noise, finer detector pixels, and low-dose limits of detectability. Theoretical results agreed quantitatively with the measured NPS and qualitatively with evaluation of cadaver images by a musculoskeletal radiologist. Conclusions: A fairly comprehensive model for 3D imaging performance in cone-beam CT combines factors of quantum noise, system geometry, anatomical background, and imaging task. The analysis provided a valuable, quantitative guide to design, optimization, and technique selection for a musculoskeletal extremities imaging system under development.

The results from simulating the variance in malignant tissue thermal and electrical properties will help guide better approximations for MWA treatments. The results suggest that assuming malignant and healthy liver tissues have similar dielectric properties is a reasonable first approximation. Antenna placement relative to the tumor has minimal impact on the absolute size of the ablation zone, yet it does cause relevant variation between desired treatment margin and ablation zone. Blood vessel cooling, especially hepatic vessels close to the region of interest, may be a significant factor to consider in treatment planning. Further data need to be collected for assessing treatment planning utility of modeling MWA in this context.

Dielectric parameters, blood perfusion rate, and the temperature interval across which the tissue changes phase were found to have the most significant impact on MWA model outputs. The latent heat of tissue water vaporization and the volumetric heat capacity of the vaporized tissue were recognized as the least influential parameters. Uncertainties in model outputs identified in this study can be incorporated to provide probabilistic maps of expected ablation outcome for patient-specific treatment planning.

Single- and dual-antenna arrays systems operating at 2.45 GHz yield larger ablation zone due to greater power deposition in proximity to the antenna, as well as greater role of thermal conduction.

Purpose-To determine the impact of including dynamic changes in tissue physical properties during heating on feedback controlled thermal ablation with catheter-based ultrasound. Additionally, we compared impact several indicators of thermal damage on predicted extents of ablation zones for planning and monitoring ablations with this modality.Methods-A 3D model of ultrasound ablation with interstitial and transurethral applicators incorporating temperature based feedback control was used to simulate thermal ablations in prostate and liver tissue. We investigated five coupled models of heat dependent changes in tissue acoustic attenuation/absorption and blood perfusion of varying degrees of complexity.. Dimensions of the ablation zone were computed using temperature, thermal dose, and Arrhenius thermal damage indicators of coagulative necrosis. A comparison of the predictions by each of these models was illustrated on a patient-specific anatomy in the treatment planning setting.Results-Models including dynamic changes in blood perfusion and acoustic attenuation as a function of thermal dose/damage predicted near-identical ablation zone volumes (maximum variation < 2.5%). Accounting for dynamic acoustic attenuation appeared to play a critical role in estimating ablation zone size, as models using constant values for acoustic attenuation predicted ablation zone volumes up to 50% larger or 47% smaller in liver and prostate tissue, respectively. Thermal dose (t 43 ≥ 240min) and thermal damage (Ω ≥ 4.6) thresholds for coagulative necrosis are in good agreement for all heating durations, temperature thresholds in the range of 54 °C for short (< 5 min) duration ablations and 50 °C for long (15 min) ablations may serve as surrogates for determination of the outer treatment boundary.Conclusions-Accounting for dynamic changes in acoustic attenuation/absorption appeared to play a critical role in predicted extents of ablation zones. For typical 5-15 min ablations with this modality, thermal dose and Arrhenius damage measures of ablation zone dimensions are in good agreement, while appropriately selected temperature thresholds provide a computationally cheaper surrogate.

BackgroundIntratumoral delivery of immunotherapeutics represents a compelling solution to directly address local barriers to tumor immunity. However, we have previously shown that off-target delivery is a substantial problem during intratumoral injections; this can lead to diminished drug efficacy and systemic toxicities. We have identified three variables that influence intratumoral drug delivery: injection technique, drug formulation and tumor microenvironment. The purpose of this study was to characterize the impact of modifications in each variable on intratumoral drug delivery and immunotherapy efficacy.MethodsIntratumoral injections were performed in a hybrid image-guided intervention suite with ultrasound, fluoroscopy and CT scanning capabilities in both rat and mouse syngeneic tumor models. Intratumoral drug distribution was quantified by CT volumetric imaging. The influence of varying needle design and hydrogel-based drug delivery on the immune response to a stimulator of interferon genes (STING) agonist was evaluated using flow cytometry and single cell RNA sequencing. We also evaluated the influence of tumor stiffness on drug injection distribution.ResultsVariations in needle design, specifically with the use of a multiside hole needle, led to approximately threefold improvements in intratumoral drug deposition relative to conventional end-hole needles. Likewise, delivery of a STING agonist through a multiside hole needle led to significantly increased expression of type I interferon-associated genes and ‘inflammatory’ dendritic cell gene signatures relative to end-hole STING agonist delivery. A multidomain peptide-based hydrogel embedded with a STING agonist led to substantial improvements in intratumoral deposition; however, the hydrogel was noted to generate a strong immune response against itself within the target tumor. Evaluation of tumor stroma on intratumoral drug delivery revealed that there was a greater than twofold improvement in intratumoral distribution in soft tumors (B16 melanoma) compared with firm tumors (MC38 colorectal).ConclusionsInjection technique, drug formulation and tumor stiffness play key roles in the accurate delivery of intratumoral immunotherapeutics.