PURPOSE:Our goal was to determine whether the difference between MRI-based and ultrasound (US)-based volume measurements are associated with MRI/US-targeted fusion-guided biopsy outcomes. MATERIALS AND METHODS:This retrospective, single-center study involved 4177 consecutive patients biopsied between 2010 and 2023 using both MRI/US-targeted fusion and systematic biopsy. Biopsies were indicated because of elevated PSA levels or abnormal multiparametric MRI results. US volume measurements were calculated using the triplane ellipsoid formula, and MRI volumes were obtained by semiautomatic planimetric segmentation. Performance of fusion biopsy compared with systematic biopsy was analyzed with respect to the discordance between MRI and US volume measurements. RESULTS:In 2736 patients (66%), biopsy detected prostate cancer. In cases where both techniques yielded prostate cancers (1695/2736 [62%]), a statistically higher proportion of patients had higher Gleason scores on MRI/US-targeted fusion biopsy compared with systematic biopsy (343 patients [20.2%] vs 137 patients [8.1%], P < .001). MRI volume measurements were significantly smaller compared with US volume measurements (median [IQR] 54 mL [39-77], 56 mL [40-80], respectively, P < .001). Beyond 5 mL volume discordance, MRI/US-targeted fusion biopsy gradually showed less added diagnostic benefit compared with systematic biopsy. In the ≤ 5 mL cohort, MRI/US-targeted fusion biopsy detected more aggressive tumors in 4 times as many patients as systematic biopsy (136 vs 32 patients, P < .001). CONCLUSIONS:Although MRI/US-targeted fusion biopsy detected more prostate cancers than systematic biopsy, the performance of MRI/US-targeted fusion biopsy declined with more discordance between volumes measured in MRI vs US. Awareness of volume discordance in MRI- and US-based volume measurements should alert the operator about the possibility of reduced performance of MRI/US-targeted fusion biopsy.

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.

With continuously rising breast augmentation procedures worldwide, there is an increasing clinical need for an early and accurate detection of implant complications. In clinical practice, silicone implants are mainly visualized by silicone-only acquisitions which can be limited by a low signal-to-noise ratio and poor resolution. The present work proposes chemical shift encoding-based multi-echo gradient-echo imaging in combination with a robust graph-cuts-based water-fat-silicone separation. The resulting multi-contrast imaging at high isotropic resolution enables a more precise delineation of the implant capsule and a better evaluation of the implant’s integrity compared to conventional silicone-only acquisition.

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.

The aim of this study was to assess the feasibility of quantifying morphologic changes in tumors during immunotherapy, as a reflection of response or survival. A retrospective single-center analysis was performed in patients with unresectable liver cancer previously enrolled in clinical trials combining immunotherapy (tremelimumab ± durvalumab) and locoregional treatment (either ablation or transarterial chemoembolization). Conventional response (RECIST 1.1) was assessed at 6-month follow-up. For morphologic assessment, the largest target lesion was manually segmented on axial slices in two dimensions using contrast-enhanced CT. Solidity and circularity of tumors were calculated at baseline, 3-month follow-up, and at 6-months follow-up. Survival analysis was performed. From the 68 patients enrolled in clinical trials, 28 did not have target lesions separate from lesions treated by locoregional therapies, and 3 had no follow-up imaging. Thirty-seven patients (9 with biliary cancer and 28 with hepatocellular carcinoma) were included. Shape features and shape variation were not correlated with RECIST 1.1 status at 6-month follow-up. However, patients with low solidity tumors at 6-month follow-up showed poorer prognosis compared with patients with high solidity tumors at 6-month follow-up (p = 0.01). Solidity variation analysis confirmed that a decrease of tumor solidity at 6-month follow-up was associated with poorer prognosis (p = 0.01). No association was found between shape features at baseline or shape features at 3-month follow-up with overall survival. Evolution and variation of tumor morphology during treatment may reflect or correlate with outcomes and contribute toward adapted response criteria.

Despite advancements in precision and efficacy of microwave ablation for tumor management, accurately predicting ablation zone geometry and minimum ablation margin remains a major challenge. This pilot study seeks to elucidate the influence of probe configuration on the morphometry of resulting ablation zones using tissue mimicking thermochromic phantoms. In-vitro results from 12 ablations were analyzed: a single probe ablation (n=1) and dual probe ablations (n=11). Angles and separations greatly influenced ablation zone morphometry. In dual-probe ablations, probe tip separation and angle of offset were positively correlated with ablation zone volume, length, and cross-sectional circularity. IR ablation planning is currently suboptimal, as it often relies upon cognitive registration. Even treatment planning software creates virtual composite ablation volumes based upon data from theoretical ablations in single, idealized configurations and settings. These findings draw attention to a need for improved ablation zone prediction and planning, which might impact efficiency, safety, cost, and outcomes.

Targeting accuracy determines outcomes for percutaneous needle interventions. Augmented reality (AR) in IR may improve procedural guidance and facilitate access to complex locations. This study aimed to evaluate percutaneous needle placement accuracy using a goggle-based AR system compared to an ultrasound (US)-based fusion navigation system. Six interventional radiologists performed 24 independent needle placements in an anthropomorphic phantom (CIRS 057A) in four needle guidance cohorts (n = 6 each): (1) US-based fusion, (2) goggle-based AR with stereoscopically projected anatomy (AR-overlay), (3) goggle AR without the projection (AR-plain), and (4) CT-guided freehand. US-based fusion included US/CT registration with electromagnetic (EM) needle, transducer, and patient tracking. For AR-overlay, US, EM-tracked needle, stereoscopic anatomical structures and targets were superimposed over the phantom. Needle placement accuracy (distance from needle tip to target center), placement time (from skin puncture to final position), and procedure time (time to completion) were measured. Mean needle placement accuracy using US-based fusion, AR-overlay, AR-plain, and freehand was 4.5 ± 1.7 mm, 7.0 ± 4.7 mm, 4.7 ± 1.7 mm, and 9.2 ± 5.8 mm, respectively. AR-plain demonstrated comparable accuracy to US-based fusion (p = 0.7) and AR-overlay (p = 0.06). Excluding two outliers, AR-overlay accuracy became 5.9 ± 2.6 mm. US-based fusion had the highest mean placement time (44.3 ± 27.7 s) compared to all navigation cohorts (p < 0.001). Longest procedure times were recorded with AR-overlay (34 ± 10.2 min) compared to AR-plain (22.7 ± 8.6 min, p = 0.09), US-based fusion (19.5 ± 5.6 min, p = 0.02), and freehand (14.8 ± 1.6 min, p = 0.002). Goggle-based AR showed no difference in needle placement accuracy compared to the commercially available US-based fusion navigation platform. Differences in accuracy and procedure times were apparent with different display modes (with/without stereoscopic projections). The AR-based projection of the US and needle trajectory over the body may be a helpful tool to enhance visuospatial orientation. Thus, this study refines the potential role of AR for needle placements, which may serve as a catalyst for informed implementation of AR techniques in IR.

Introduction and Objectives: Although unlimited sessions of conventional transarterial chemoembolization (cTACE) may be performed for liver metastases, there is no data indicating when treatment becomes ineffective. This study aimed to determine the optimal number of repeat cTACE sessions for nonresponding patients before abandoning cTACE in patients with liver metastases. Materials and Methods: In this retrospective, single-institutional analysis, patients with liver metastases from neuroendocrine tumors (NET), colorectal carcinoma (CRC), and lung cancer who underwent consecutive cTACE sessions from 2001 to 2015 were studied. Quantitative European Association for Study of the Liver (qEASL) criteria were utilized for response assessment. The association between the number of cTACE and 2-year, 5-year, and overall survival was evaluated to estimate the optimal number of cTACE for each survival outcome. Results: Eighty-five patients underwent a total of 186 cTACE sessions for 117 liver metastases, of which 30.7 % responded to the first cTACE. For the target lesions that did not respond to the first, second, and third cTACE sessions, response rates after the second, third, and fourth cTACE sessions were 33.3 %, 23%, and 25%, respectively. The fourth cTACE session was the optimal numberfor 2-year survival (HR0.40; 95 %CI: 0.16-0.97; p=0.04), 5-year survival (HR0.31; 95 %CI: 0.11-0.87; p =0.02), and overall survival(HR0.35; 95 %CI: 0.13-0.89; p = 0.02). Conclusions: Repeat cTACE in the management of liver metastases from NET, CRC, and lung cancer was associated with improved patient survival. We recommend at least four cTACE sessions before switching to another treatment for nonresponding metastatic liver lesions. (c) 2024 Fundaci & oacute;n Cl & iacute;nica M & eacute;dica Sur, A.C. Published by Elsevier Espa & ntilde;a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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.

PurposeTo (a) develop a preconditioned water-fat-silicone total field inversion (wfsTFI) algorithm that directly estimates the susceptibility map from complex multi-echo data in the breast in the presence of silicone and to (b) evaluate the performance of wfsTFI for breast quantitative susceptibility mapping (QSM) in silico and in vivo in comparison with formerly proposed methods. MethodsNumerical simulations and in vivo multi-echo gradient echo breast measurements were performed to compare wfsTFI to a previously proposed field map-based linear total field inversion algorithm (lTFI) with and without the consideration of the chemical shift of silicone in the field map estimation step. Specifically, a simulation based on an in vivo scan and data from five patients were included in the analysis. ResultsIn the simulation, wfsTFI is able to significantly decrease the normalized root mean square error from lTFI without (4.46) and with (1.77) the consideration of the chemical shift of silicone to 0.68. Both the in silico and in vivo wfsTFI susceptibility maps show reduced shadowing artifacts in local tissue adjacent to silicone, reduced streaking artifacts and no erroneous single voxels of diamagnetic susceptibility in proximity to silicone. ConclusionThe proposed wfsTFI method can automatically distinguish between subjects with and without silicone. Furthermore wfsTFI accounts for the presence of silicone in the QSM dipole inversion and allows for the robust estimation of susceptibility in proximity to silicone breast implants and hence allows the visualization of structures that would otherwise be dominated by artifacts on susceptibility maps.

A water- and fat-suppressed sequence is typically used to verify the integrity of silicone breast implants. The feasibility of using chemical shift encoding-based MRI for in vivo water–fat–silicone separation was recently shown. In this work, a hierarchical multi-resolution graph-cut framework is developed and proposed for water–fat–silicone separation in breast MRI. Robustness and competitive processing times are achieved by performing graph-cuts using varying spatial resolution. Results show successful water–fat–silicone separation for 4 echoes (the minimum of required echoes) without water–fat–silicone swaps and an improved silicone contrast compared to the conventional sequence.

Conventional methods for semi-automatic and rule-based breast segmentation on MR images have a tradeoff between accuracy and segmentation speed. To overcome this, several 2D-deep learning approaches have been proposed, which usually focus on using T1-weighted images to train their models. Our aim is to train a 3D-network for breast segmentation, trained on water-fat MR images, which can be used to measure the breast density based on the proton density fat fraction (PDFF). We show that our model segments both fast and accurately, and can visually outperform our ground truth segmentations while requiring only a few seconds to generate labels.

Early stage malignant tumors are often accompanied by microcalcifications. X-ray-based mammography examinations are routinely used for screening and early detection due to the excellent contrast of calcified structures. However, due to the damaging nature of x-ray radiation, the use of an MR-based technique would be desirable for repeated examinations. In this work, we present initial results of quantitative-susceptibility-mapping-based (QSM) mammography-like MR-images that show robust detection of calcifications down to the resolution of the MR scan. Furthermore, the proposed method accounts for the potential presence of silicone breast implants allowing robust QSM in proximity to silicone implants for the first time.

Water-fat separation is a non-linear non-convex parameter estimation problem in magnetic resonance imaging typically solved using spatial constraints. However, there is still limited knowledge on how to separate in vivo three chemical species in the presence of magnetic field inhomogeneities. The proposed method uses multiple graph-cuts in a hierarchical multi-resolution framework to perform robust chemical species separation in the breast for subjects with and without silicone implants. Experimental results show that the proposed method can decrease the computational time for water-fat separation and perform accurate water-fat-silicone separation with only a limited number of acquired echo images at 3 T. The silicone-separated images have an improved spatial resolution and image contrast compared to conventional scans used for regular monitoring of the silicone implant's integrity.

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm3 or ETB below 4% were reassigned to BCLC Bn, whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC Cn by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC Bn class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC Cn group) (n = 222; ETV ≥65 cm3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article.

There is a clinical need for a non-ionizing, quantitative assessment of breast density, as one of the strongest independent risk factors for breast cancer. This study aims to establish proton density fat fraction (PDFF) as a quantitative biomarker for fat tissue concentration in breast MRI and correlate mean breast PDFF to mammography. In this retrospective study, 193 women were routinely subjected to 3-T MRI using a six-echo chemical shift encoding-based water-fat sequence. Water-fat separation was based on a signal model accounting for a single T2* decay and a pre-calibrated 7-peak fat spectrum resulting in volumetric fat-only, water-only images, PDFF- and T2*-values. After semi-automated breast segmentation, PDFF and T2* values were determined for the entire breast and fibroglandular tissue. The mammographic and MRI-based breast density was classified by visual estimation using the American College of Radiology Breast Imaging Reporting and Data System categories (ACR A-D). The PDFF negatively correlated with mammographic and MRI breast density measurements (Spearman rho: −0.74, p < .001) and revealed a significant distinction between all four ACR categories. Mean T2* of the fibroglandular tissue correlated with increasing ACR categories (Spearman rho: 0.34, p < .001). The PDFF of the fibroglandular tissue showed a correlation with age (Pearson rho: 0.56, p = .03). The proposed breast PDFF as an automated tissue fat concentration measurement is comparable with mammographic breast density estimations. Therefore, it is a promising approach to an accurate, user-independent, and non-ionizing breast density assessment that could be easily incorporated into clinical routine breast MRI exams. • The proposed PDFF strongly negatively correlates with visually determined mammographic and MRI-based breast density estimations and therefore allows for an accurate, non-ionizing, and user-independent breast density measurement. • In combination with T2*, the PDFF can be used to track structural alterations in the composition of breast tissue for an individualized risk assessment for breast cancer.

Purpose: To characterize the effects of commonly used transcatheter arterial chemoembolization (TACE) regimens on the immune response and immune checkpoint marker expression using a VX2 rabbit liver tumor model. Materials and Methods: Twenty-four VX2 liver tumor-bearing New Zealand white rabbits were assigned to 7 groups (n = 3 per group) undergoing locoregional therapy as follows: (a) bicarbonate infusion without embolization, (b) conventional TACE (cTACE) using a water-in-oil emulsion containing doxorubicin mixed 1:2 with Lipiodol, drug-eluting embolic-TACE with either (c) idarubicin-eluting Oncozene microspheres (40 mu m) or (d) doxorubicin-eluting Lumi beads (40-90 mu m). For each therapy arm (b-d), a tandem set of 3 animals with additional bicarbonate infusion before TACE was added, to evaluate the effect of pH modification on the immune response. Three untreated rabbits served as controls. Tissue was harvested 24 hours after treatment, followed by digital immunohistochemistry quantification (counts/mu m(2) +/- SEM) of tumor-infiltrating cluster of differentiation 3+ T-lymphocytes, human leukocyte antigen DR type antigen-presenting cells (APCs), cytotoxic T-lymphocyteassociated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway axis expression. Results: Lumi-bead TACE induced significantly more intratumoral T-cell and APC infiltration than cTACE and Oncozene-microsphere TACE. Additionally, tumors treated with Lumi-bead TACE expressed significantly higher intratumoral immune checkpoint markers compared with cTACE and Oncozene-microsphere TACE. Neoadjuvant bicarbonate demonstrated the most pronounced effect on cTACE and resulted in a significant increase in intratumoral cluster of differentiation 3+ T-cell infiltration compared with cTACE alone. Conclusions: This preclinical study revealed significant differences in evoked tumor immunogenicity depending on the choice of chemoembolic regimen for TACE.

The goal of this study was to investigate the effects of TACE using Lipiodol, Oncozene™ drug-eluting embolics (DEEs), or LUMI™-DEEs alone, or combined with bicarbonate on the metabolic and immunological tumor microenvironment in a rabbit VX2 tumor model. VX2 liver tumor-bearing rabbits were assigned to five groups. MRI and extracellular pH (pHe) mapping using Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) were performed before and after intra-arterial therapy with conventional TACE (cTACE), DEE-TACE with Idarubicin-eluting Oncozene™-DEEs, or Doxorubicin-eluting LUMI™-DEEs, each with or without prior bicarbonate infusion, and in untreated rabbits or treated with intra-arterial bicarbonate only. Imaging results were validated with immunohistochemistry (IHC) staining of cell viability (PCNA, TUNEL) and immune response (HLA-DR, CD3). Statistical analysis was performed using Mann–Whitney U test. pHe mapping revealed that combining cTACE with prior bicarbonate infusion significantly increased tumor pHe compared to control (p = 0.0175) and cTACE alone (p = 0.0025). IHC staining revealed peritumoral accumulation of HLA-DR+ antigen-presenting cells and CD3 + T-lymphocytes in controls. cTACE-treated tumors showed reduced immune infiltration, which was restored through combination with bicarbonate. DEE-TACE with Oncozene™-DEEs induced moderate intratumoral and marked peritumoral infiltration, which was slightly reduced with bicarbonate. Addition of bicarbonate prior to LUMI™-beads enhanced peritumoral immune cell infiltration compared to LUMI™-beads alone and resulted in the strongest intratumoral immune cell infiltration across all treated groups. The choice of chemoembolic regimen for TACE strongly affects post-treatment TME pHe and the ability of immune cells to accumulate and infiltrate the tumor tissue. • Combining conventional transarterial chemotherapy with prior bicarbonate infusion increases the pHe towards a more physiological value (p = 0.0025). • Peritumoral infiltration and intratumoral accumulation patterns of antigen-presenting cells and T-lymphocytes after transarterial chemotherapy were dependent on the choice of the chemoembolic regimen. • Combination of intra-arterial treatment with Doxorubicin-eluting LUMI™-beads and bicarbonate infusion resulted in the strongest intratumoral presence of immune cells (positivity index of 0.47 for HLADR+-cells and 0.62 for CD3+-cells).

Purpose: To investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-mu m and 100-mu m drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model. Materials and Methods: Twelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-mu m (n = 5) or 100-mu m (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24-72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusionweighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia. Laboratory parameters and histopathologic ex vivo analysis included fluorescence confocal microscopy and immunohistochemistry. increases in diffusion across the entire lesion (apparent diffusion coefficient, 1.89 x 10(-3) mm(2)/s +/- 0.18 vs 2.34 x 10(-3) mm(2)/s +/- 0.18 in liver; P = .002). BIRDS demonstrated profound tumor acidosis at baseline (mean pHe, 6.79 +/- 0.08 in tumor vs 7.13 +/- 0.08 in liver; P = .02) and after chemoembolization (6.8 +/- 0.06 in tumor vs 7.1 +/- 0.04 in liver; P = .007). Laboratory and ex vivo analyses showed central tumor core penetration and greater increase in liver enzymes for 40-mu m vs 100-mu m microspheres. Inhibition of cell proliferation, intratumoral hypoxia, and limited idarubicin elution were equally observed with both sphere sizes. Conclusions: Noninvasive multiparametric MR imaging visualized chemoembolic effects in tumor and tumor microenvironment following DEE chemoembolization. Devascularization, increased hypoxia, coagulative necrosis, tumor acidosis, and limited idarubicin elution suggest ischemia as the predominant therapeutic mechanism. Substantial size-dependent differences indicate greater toxicity with the smaller microsphere diameter.

To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic resonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand white rabbits with hepatic VX2 tumors were examined by MRI at different time points following tumor implantation (day 14, 21, 28). A steady-state precession readout single-shot MOLLI sequence was acquired in a 3 T MRI scanner in prone position using a head-neck coil. The tumors were segmented into a central, marginal, and peritumoral region in anatomical images and color-coded T1 maps. In histopathological sections, stained with H&E and Picrosirius red, the regions corresponded to central tumor necrosis and accumulation of viable cells with fibrosis in the tumor periphery. Another region of interest (ROI) was placed in healthy liver tissue. T1 times were correlated with quantitative data of collagen area staining. A two-way repeated-measures ANOVA was used to compare cohorts and tumor regions. Hepatic tumors were successfully induced in all rabbits. T1 mapping demonstrated significant differences between the different tumor regions (F(1.43,34.26) = 106.93, p < 0.001) without interaction effects between time points and regions (F(2.86,34.26) = 0.74, p = 0.53). In vivo T1 times significantly correlated with ex vivo collagen stains (area %), (center: r = 0.78, p < 0.001; margin: r = 0.84, p < 0.001; peritumoral: r = 0.73, p < 0.001). Post hoc tests using Sidak's correction revealed significant differences in T1 times between all three regions (p < 0.001). Native T1 mapping is feasible and allows the differentiation of tumor regions based on ECM composition in a longitudinal tumor study in an experimental small animal model, making it a potential quantitative biomarker of ECM remodeling and a promising technique for future treatment studies.