Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy : A retrospective study.

PURPOSE: Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. METHODS: In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. RESULTS: SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2­Gy fractions with α/ß 10 Gy (EQD2α/ß10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/ß3-8 dose to the liver (12.8-12.6) with a 10% likelihood of ncRILD. CONCLUSION: SBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61-73.1 Gy, coupled with a mean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Reduction of ADC bias in diffusion MRI with deep learning-based acceleration: A phantom validation study at 3.0 T.

PURPOSE: Further acceleration of DWI in diagnostic radiology is desired but challenging mainly due to low SNR in high b-value images and associated bias in quantitative ADC values. Deep learning-based reconstruction and denoising may provide a solution to address this challenge. METHODS: The effects of SNR reduction on ADC bias and variability were investigated using a commercial diffusion phantom and numerical simulations. In the phantom, performance of different reconstruction methods, including conventional parallel (SENSE) imaging, compressed sensing (C-SENSE), and compressed SENSE acceleration with an artificial intelligence deep learning-based technique (C-SENSE AI), was compared at different acceleration factors and flip angles using ROI-based analysis. ADC bias was assessed by Lin's Concordance correlation coefficient (CCC) followed by bootstrapping to calculate confidence intervals (CI). ADC random measurement error (RME) was assessed by the mean coefficient of variation (CV¯) and non-parametric statistical tests. RESULTS: The simulations predicted increasingly negative bias and loss of precision towards lower SNR. These effects were confirmed in phantom measurements of increasing acceleration, for which CCC decreased from 0.947 to 0.279 and CV¯ increased from 0.043 to 0.439, and of decreasing flip angle, for which CCC decreased from 0.990 to 0.063 and CV¯ increased from 0.037 to 0.508. At high acceleration and low flip angle, C-SENSE AI reconstruction yielded best denoised ADC maps. For the lowest investigated flip angle, CCC = {0.630, 0.771 and 0.987} and CV¯={0.508, 0.426 and 0.254} were obtained for {SENSE, C-SENSE, C-SENSE AI}, the improvement by C-SENSE AI being significant as compared to the other methods (CV: p = 0.033 for C-SENSE AI vs. C-SENSE and p < 0.001 for C-SENSE AI vs. SENSE; CCC: non-overlapping CI between reconstruction methods). For the highest investigated acceleration factor, CCC = {0.479,0.926,0.960} and CV¯={0.519,0.119,0.118} were found, confirming the reduction of bias and RME by C-SENSE AI as compared to C-SENSE (by trend) and to SENSE (CV: p < 0.001; CCC: non-overlapping CI). CONCLUSION: ADC bias and random measurement error in DWI at low SNR, typically associated with scan acceleration, can be effectively reduced by deep-learning based C-SENSE AI reconstruction.

Liver diffusion-weighted MR imaging with L1-regularized iterative sensitivity encoding reconstruction based on single-shot echo-planar imaging: initial clinical experience.

To investigate whether combining L1-regularized iterative sensitivity encoding (SENSE) reconstruction and single-shot echo planar imaging (EPI) is useful in hepatic DWI. Single-shot EPI-DWI with L1-regularized iterative SENSE reconstruction (L1-DWI) and conventional parallel imaging-based reconstruction (conv-DWI) in liver MRI were compared in volunteers and patients. For the patient cohort, 75 subjects (60 ± 13 years) with 349 focal liver lesions (FLL) were included. Patient groups A and B were used to reduce acquisition time or improve spatial resolution, respectively. Image parameters were rated on a 5-point scale. The number of FLLs was recorded; in case of discrepancy, the reason for non-detectability was analyzed. In volunteers, higher signal-to-noise ratio (24.4 ± 5.6 vs. 12.2 ± 2.3, p < 0.001 at b = 0; 19.3 ± 2.8 vs. 9.8 ± 1.6, p < 0.001 at b = 800) and lower standard deviation of the apparent diffusion coefficient-values (0.17 vs. 0.20 mm2/s, p < 0.05) were found on L1-DWI compared to conv-DWI. In patients, image ratings were similar for all parameters except for "conspicuity of FLLs" which was rated significantly lower on L1-DWI vs. conv-DWI (4.7 ± 0.6 vs. 4.2 ± 0.9, p < 0.05) in group A. In five patients, 11/349 FLLs were not detectable on L1-DWI, but on conv-DWI. L1-regularized iterative reconstruction of single-shot EPI DWI can accelerate image acquisition or improve spatial resolution. However, our finding that FLLs were non-detectable on L1-DWI warrants further research.

Recurrent Colorectal Liver Metastases in the Liver Remnant After Major Liver Surgery-IRE as a Salvage Local Treatment When Resection and Thermal Ablation are Unsuitable.

PURPOSE: To examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation. PATIENTS AND METHODS: Twenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively. RESULTS: Complete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases. CONCLUSION: In this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable.

MRI-Based Quantitation of Hepatic Steatosis Does Not Predict Hypertrophy Rate after Portal Vein Embolization in Patients with Colorectal Liver Metastasis and Normal to Moderately Elevated Fat Fraction.

The aim of this study was to correlate the pre-procedural magnetic-resonance-imaging-based hepatic fat fraction (hFF) with the degree of hypertrophy after portal vein embolization (PVE) in patients with colorectal cancer liver metastases (CRCLM). Between 2011 November and 2020 February, 68 patients with CRCLM underwent magnetic resonance imaging (MRI; 1.5 Tesla) of the liver before PVE. Using T1w chemical shift imaging (DUAL FFE), the patients were categorized as having a normal (<5%) or an elevated (>5%) hFF. The correlation of hFF, age, gender, initial tumor mass, history of chemotherapy, degree of liver hypertrophy, and kinetic growth rate after PVE was investigated using multiple regression analysis and Spearman's test. A normal hFF was found in 43/68 patients (63%), whereas 25/68 (37%) patients had an elevated hFF. The mean hypertrophy and kinetic growth rates in patients with normal vs. elevated hFF were 24 ± 31% vs. 28 ± 36% and 9 ± 9 % vs. 8 ± 10% (p > 0.05), respectively. Spearman's test showed no correlation between hFF and the degree of hypertrophy (R = -0.04). Multivariable analysis showed no correlation between hFF, history of chemotherapy, age, baseline tumor burden, or laterality of primary colorectal cancer, and only a poor inverse correlation between age and kinetic growth rate after PVE. An elevated hFF in a pre-procedural MRI does not correlate with the hypertrophy rate after PVE and should therefore not be used as a contraindication to the procedure in patients with CRCLM.

Intraoperative Transfusion of Fresh Frozen Plasma Predicts Morbidity Following Partial Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: The reduction of perioperative morbidity is a main surgical goal in patients undergoing partial hepatectomy for hepatocellular carcinoma (HCC). Here, we investigated clinical determinants of perioperative morbidity in a European cohort of patients undergoing surgical resection for HCC. METHODS: A total 136 patients who underwent partial hepatectomy for HCC between 2011 and 2017 at our institution were included in this analysis. The associations between major surgical complications (Clavien-Dindo ≥ 3) and overall morbidity (Clavien-Dindo ≥ 1) with clinical variables were assessed using univariate and multivariable binary logistic regression analysis. RESULTS: Multivariable analysis identified the Child-Pugh-Score (CPS, HR = 3.23; p = 0.040), operative time (HR = 5.63; p = 0.003), and intraoperatively administered fresh frozen plasma (FFP, HR = 5.62; p = 0.001) as independent prognostic markers of major surgical complications, while only FFP (HR = 6.52; p = 0.001) was associated with morbidity in the multivariable analysis. The transfusion of FFP was not associated with perioperative liver functions tests. CONCLUSIONS: The intraoperative administration of FFP is an important independent predictor of perioperative morbidity in patients undergoing partial hepatectomy for HCC.

Irreversible Electroporation for Hepatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

PURPOSE: A consensus study of panelists was performed to provide a uniform protocol regarding (contra) indications, procedural parameters, perioperative care, and follow-up of irreversible electroporation (IRE) for the treatment of hepatic malignancies. MATERIALS AND METHODS: Interventional radiologists who had 2 or more publications on IRE, reporting at least 1 patient cohort in the field of hepatobiliary IRE, were recruited. The 8 panelists were asked to anonymously complete 3 iterative rounds of IRE-focused questionnaires to collect data according to a modified Delphi technique. Consensus was defined as having reached 80% or greater agreement. RESULTS: Panel members' response rates were 88%, 75%, and 88% in rounds 1, 2, and 3, respectively; consensus was reached on 124 of 136 items (91%). Percutaneous or intraoperative hepatic IRE should be considered for unresectable primary and secondary malignancies that are truly unsuitable for thermal ablation because of proximity to critical structures. Absolute contraindications are ventricular arrhythmias, cardiac stimulation devices, and congestive heart failure of New York Heart Association class 3 or higher. A metal stent outside the ablation zone should not be considered a contraindication. For the only commercially available IRE device, the recommended settings are an inter-electrode distance of 10-20 mm and an exposure length of 20 mm. After 10 test pulses, 90 treatment pulses of 1500 V/cm should be delivered continuously, with a pulse length of 70-90 µs. The first post-procedural follow-up should take place 1 month after IRE and thereafter every 3 months, using cross-sectional imaging plus tumor marker assessment. CONCLUSIONS: This article provides recommendations, created by a modified Delphi consensus study, regarding patient selection, workup, procedure, and follow-up of IRE treatment for hepatic malignancies.

Signal changes in T2-weighted MRI of liver metastases under bevacizumab-A practical imaging biomarker?

OBJECTIVE: The purpose of this study was to investigate signal changes in T2-weighted magnetic resonance imaging of liver metastases under treatment with and without bevacizumab-containing chemotherapy and to compare these signal changes to tumor contrast enhancement. MATERIALS AND METHODS: Retrospective analysis of 44 patients, aged 36-84 years, who underwent liver magnetic resonance imaging including T2-weighted and dynamic contrast enhancement sequences. Patients received bevacizumab-containing (n = 22) or conventional cytotoxic chemotherapy (n = 22). Magnetic resonance imaging was obtained at baseline and at three follow-ups (on average 3, 6 and 9 months after initial treatment). Three independent readers rated the T2 signal intensity and the relative contrast enhancement of the metastases on a 5-point scale. RESULTS: T2 signal intensity of metastases treated with bevacizumab showed a significant (p<0.001) decrease in T2 signal intensity after initial treatment and exhibit compared to conventionally treated metastases significantly (p<0.001 for each follow-up) hypointense (bevacizumab: 0.70 ± 0.83 before vs. -1.55 ± 0.61, -1.91 ± 0.62, and -1.97 ± 0.52; cytotoxic: 0.73 ± 0.79 before vs. -0.69 ± 0.81, -0.71 ± 0.68, and -0.75 ± 0.65 after 3, 6, and 9 months, respectively). T2 signal intensity was strongly correlated with tumor contrast enhancement (r = 0.71; p<0.001). Intra-observer agreement for T2-signal intensity was substantial (κ = 0.75). The agreement for tumoral contrast enhancement between the readers was considerably lower (κ = 0.39). CONCLUSION: Liver metastases exhibit considerably hypointense in T2-weighted imaging after treatment with bevacizumab, in contrast to conventionally treated liver metastases. Therefore, T2-weighted imaging seems to reflect the effect of bevacizumab.

A New Model for MR Evaluation of Liver Function with Gadoxetic Acid, Including Both Uptake and Excretion.

OBJECTIVES: Most existing models that are in use to model hepatic function through assessment of hepatic gadoxetic acid enhancement kinetics do not consider quantitative measures of gadoxetic excretion. We developed a model that allows a simultaneous quantitation of uptake and excretion of liver specific contrast agents. The aim was to improve the assessment of hepatic synthetic function, and provide quantitative measures of hepatic excretion function. METHODS: Sixteen patients underwent dynamic T1-weighted turbo gradient echo imaging at 1.5 T prior and after bolus injection of gadoxetic acid at 0.1 ml/kg. DCE-images were obtained for 30 min after injection. A dual-inlet two-compartment model was then used to fit the measured liver signal values. Four tissue parameters (extracellular volume fraction, arterial flow fraction, uptake rate and excretion half-time) were extracted for each liver segment. RESULTS: The proposed model provided a good fit to acquired data. Mean values for arterial flow fraction (0.08+-0.04), extracellular volume (0.20±0.08) and uptake rate (4.02 ±1.32 /100 ml/min) were comparable to those obtained with the conventional model (0.08±0.05, 0.21±0.12, and 4.93±1.74), but exhibited significantly less variation and improved fit quality. CONCLUSIONS: The proposed model is more accurate than existing conventional models and provides an additional excretion parameter. KEY POINTS: • Models of hepatic contrast agent uptake can be extended to include excretion. • Including an additional excretion parameter improves accuracy of the model. • Standard diagnostic sequences can be extended to incorporate the model.

Electroporation of the Liver: More Than 2 Concurrently Active, Curved Electrodes Allow New Concepts for Irreversible Electroporation and Electrochemotherapy.

Irreversible electroporation and electrochemotherapy are 2 innovative electroporation-based minimally invasive therapies for the treatment of cancer. Combining nonthermal effects of irreversible electroporation with local application of chemotherapy, electrochemotherapy is an established treatment modality for skin malignancies. Since the application of electrochemotherapy in solid organs is a promising approach, this article describes a novel electrode configuration and field generating method. For the treatment of hepatic malignancies, the shape of the electric field should resemble a spherical 3-dimensional geometry around the target tissue inside the liver. To adapt the actual shape of the field, the probe is designed in computer-aided design with a live link to a computer simulation software: Changes in design can be revalued quickly, regarding different quality criteria for field strength inside and outside the tumor. To rate these criteria, a set of formulas with weighting coefficients has been included. As a result of this design process, a needle-shaped prototype applicator has been built, designed for an intracorporal electroporation-based treatment. It can be used as percutaneous, image-guided, minimally invasive treatment option for malignant liver tumors. The shaft of the probe is used as central electrode and fitted with additional 4 expandable electrodes. These satellite electrodes are hollow, thus serving as injectors for chemotherapeutic agents within the area of the electric field. This configuration can be used for electrochemotherapy as well as irreversible electroporation. By placing 5 electrodes with just one needle, the procedure duration as well as the radiation dose can be reduced tremendously. Additionally, the probe offers an option to adapt the field geometry to the tumor geometry by connecting the 5 electrodes to 5 individually chosen electric potentials: By fine-tuning the ablation zone via the potentials instead of adjusting the location of the electrode(s), the procedure duration as well as the radiation dose will decrease further.

Diffusion-weighted MRI Is Superior to PET/CT in Predicting Survival of Patients Undergoing 90Y Radioembolization of Hepatic Metastases.

Purpose To determine the relationship between diffusion-weighted (DW) liver MR images obtained 4-6 weeks after lobar yttrium 90 (90Y) treatment and overall survival in comparison with PET/CT or established oncologic factors known to affect survival. Materials and Methods The institutional review board approved this prospective intraindividual comparative study in 36 consecutive patients (25 women) with liver-dominant metastases (20 colorectal, 14 breast, two other) (mean age, 60 years ± 10 [standard deviation]) who underwent fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT and DW MRI before and 4-6 weeks after 90Y radioembolization. DW MRI response was defined as a mean minimal apparent diffusion coefficient increase of more than 30%; PET/CT response was defined as a mean maximal standardized uptake value decrease of more than 30%. Kaplan-Meier curves, log-rank test, and multivariable Cox regression analyses were used to compare patient survival as a function of imaging and Response Evaluation Criteria in Solid Tumors (RECIST) response, pretreatment Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1), hepatic tumor load (<25% vs ≥25%), and presence versus absence of extrahepatic disease. Results Thirty-five of the 36 patients were observed until death (median survival, 36 weeks). Response was observed with PET/CT in 18 of 36 patients (50%). Median survival was 39 weeks in patients who responded to PET/CT versus 27 weeks in those who did not (P = .60). Response was observed with DW MRI in 24 of 36 patients (67%). Median survival was 53 weeks in DW MRI responders versus 20 weeks in nonresponders (P = .01). At multivariable analysis, DW MRI response was the only independent predictor of survival (P < .01). Response based on RECIST parameters, ECOG PS, hepatic tumor load, and presence of extrahepatic metastases did not correlate with survival. Conclusion In patients with hepatic metastases undergoing 90Y radioembolization, prediction of response to therapy with DW MRI was superior to that with PET/CT and established oncologic factors.

Midterm Safety and Efficacy of Irreversible Electroporation of Malignant Liver Tumors Located Close to Major Portal or Hepatic Veins.

Purpose To investigate the efficacy and safety of irreversible electroporation (IRE) in the treatment of hepatic tumors not suitable for thermal ablation (radiofrequency ablation [RFA] or microwave ablation). Materials and Methods This was an institutional review board-approved prospective study in 29 patients (15 men, 14 women; mean age, 63 years ± 12 [standard deviation]) with 43 primary (n = 8) or secondary (n = 35) malignant liver tumors who underwent computed tomography (CT)-guided IRE. All target tumors were located immediately adjacent to major hepatic veins, portal veins, or both; thus, they were not considered suitable for RFA or microwave ablation. Patients underwent postinterventional CT and magnetic resonance (MR) imaging. Systematic follow-up MR imaging was performed for 24 months on average to assess complete ablation, intrahepatic tumor recurrence, and complications. The 95% confidence intervals (CIs) were determined for the rate of bile duct strictures, incomplete ablation, and tumor recurrence. Results Complete ablation was achieved in 40 (93%; 95% CI: 85, 100) of 43 target tumors, with a safety margin of 5-10 mm, and was confirmed at immediate postinterventional CT and MR imaging. In 13 (33%; 95% CI: 18, 47) of 40 completely ablated tumors, intrahepatic tumor recurrence was observed at 2-18 months. However, only two (15%; 95% CI: 0, 35) of these 13 tumors were observed within the ablation zone. In the remaining 11 (85%; 95% CI: 65, 100), tumor growth was observed alongside the needle tract. None of the two true local recurrences occurred at the site of the vessel. All adjacent vessels remained perfused at follow-up. Five (24%; 95% CI: 5, 39) of 21 patients with target tumors adjacent to portal veins developed mild to moderate cholestasis 2-6 weeks after IRE. Conclusion IRE is useful to avoid incomplete ablation secondary to heat-sink effects and damage to major blood vessels; however, needle tract seeding is observed in 26% of treated tumors, and IRE induces sufficient local heating to bile ducts in 24% of ablations. © RSNA, 2017.

Magnetic Resonance Imaging Findings After Percutaneous Irreversible Electroporation of Liver Metastases: A Systematic Longitudinal Study.

OBJECTIVE: The aim of this study was to systematically investigate the course of magnetic resonance (MR) signal intensity (SI) changes that occur in noncirrhotic livers after irreversible electroporation (IRE) of liver metastases. METHODS: This study is an institutional review board-approved prospective longitudinal follow-up study on 27 patients with 37 liver metastases who underwent computed tomography-guided percutaneous IRE and a standardized follow-up protocol by serial hepatic MR imaging studies that consisted of a gadobutrol-enhanced dynamic series, axial T2-weighted (T2w) turbo spin echo, and diffusion-weighted imaging (b = 0/50/800), acquired before, within 2, and at 24 hours after IRE; at 1, 2, 4, 6, 8, and 12 weeks after IRE; and every 3 months thereafter for a follow-up of at least 12 months. RESULTS: The ablated target lesion remained visible within the ablation zone in 23 (62%) of 37 of cases for a mean time of 21 ± 20 weeks (median, 12 weeks). The ablation zone appeared homogeneously hyperintense on T2w turbo spin echo images on the day of IRE in 37 of 37 cases. By 24 hours after IRE, the ablation zone inverted its SI in 35 of 37 cases to intermediately hypointense, with a rim of T2w bright SI that exhibited arterial phase enhancement; this persisted for 7 ± 5 weeks (median, 4 weeks). The rim resolved in 35 (95%) of 37 cases within 3 months. The ablation zone increased slightly over the first 48 hours, then shrank progressively. Complete healing of the ablation zone was observed in 57% (21/37) after an average of 14 ± 15 (median, 8 weeks).Average apparent diffusion coefficient values of the ablation zone decreased from 0.74 ± 0.36 × 10 mm/s pre-IRE to 0.63 ± 0.27 × 10 mm/s within the first 24 hours (P < 0.05), followed by a progressive normalization to 0.91 ± 0.30 × 10 mm/s at 2 months. CONCLUSIONS: Knowledge of the broad spectrum of MR imaging findings after IRE is important to avoid diagnostic errors in the follow-up of patients after IRE.

Diagnostic accuracy of diffusion-weighted magnetic resonance imaging versus positron emission tomography/computed tomography for early response assessment of liver metastases to Y90-radioembolization.

OBJECTIVES: Patients with hepatic metastases who are candidates for Y90-radioembolization (Y90-RE) usually have advanced tumor stages with involvement of both liver lobes. Per current guidelines, these patients have usually undergone several cycles of potentially hepatotoxic systemic chemotherapy before Y90-RE is at all considered, requiring split (lobar) treatment sessions to reduce hepatic toxicity. Assessing response to Y90-RE early, that is, already after the first lobar session, would be helpful to avoid an ineffective and potentially hepatotoxic second lobar treatment. We investigated the accuracy with which diffusion- weighted magnetic resonance imaging (DWI-MRI) and positron emission tomography/computed tomography (PET/CT) can provide this information. METHODS: An institutional review board-approved prospective intraindividual comparison trial on 35 patients who underwent fluorodeoxyglucose PET/CT and DWI-MRI within 6 weeks before and 6 weeks after Y90-RE to treat secondary-progressive liver metastases from solid cancers (20 colorectal, 13 breast, 2 other) was performed. An increase of minimal apparent diffusion coefficient (ADCmin) or decrease of maximum standard uptake value (SUVmax) by at least 30% was regarded as positive response. Long-term clinical and imaging follow-up was used to distinguish true- from false-response classifications. RESULTS: On the basis of long-term follow-up, 23 (66%) of 35 patients responded to the Y90 treatment. No significant changes of metastases size or contrast enhancement were observable on pretreatment versus posttreatment CT or magnetic resonance images.However, overall SUVmax decreased from 8.0 ± 3.9 to 5.5 ± 2.2 (P < 0.0001), and ADCmin increased from 0.53 ± 0.13 × 10(-3) mm2/s to 0.77 ± 0.26 × 10(-3) mm2/s (P < 0.0001). Pretherapeutic versus posttherapeutic changes of ADCmin and SUVmax correlated moderately (r = -0.53). In 4 of the 35 patients (11%), metastases were fluorodeoxyglucose-negative such that no response assessment was possible by PET. In 25 (71%) of the 35 patients, response classification by PET and DWI-MRI was concordant; in 6 (17%) of the 35, it was discordant. In 5 of the 6 patients with discordant classifications, follow-up confirmed diagnoses made by DWI. The positive predictive value to predict response was 22 (96%) of 23 for MRI and 15 (88%) of 17 for PET. The negative predictive value to predict absence was 11 (92%) of 12 for MRI and 10 (56%) of 18 for PET. Sensitivity for detecting response was significantly higher for MRI (96%; 22/23) than for PET (65%; 15/23) (P < 0.02). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging appears superior to PET/CT for early response assessment in patients with hepatic metastases of common solid tumors. It may be used in between lobar treatment sessions to guide further management of patients who undergo Y90-RE for hepatic metastases.

Assessment of BI-RADS category 4 lesions detected with screening mammography and screening US: utility of MR imaging.

PURPOSE: To investigate the utility of magnetic resonance (MR) imaging according to different types of Breast Imaging Reporting and Data System (BI-RADS) category 4 findings from screening mammography and/or screening ultrasonography (US). MATERIALS AND METHODS: This institutional review board-approved prospective study included 340 patients in whom 353 lesions were detected at screening mammography or US and were rated BI-RADS category 4 after appropriate conventional work-up. Written informed consent was obtained from all patients. Women underwent standard dynamic contrast material-enhanced MR imaging for further assessment. Women with negative or benign MR findings who did not proceed to biopsy underwent intensified follow-up for at least 18 months. Pure clustered microcalcifications were followed up for at least 24 months. RESULTS: Of the 353 study findings, 66 (18.7%) were finally shown to be true-positive (23 cases of ductal carcinoma in situ [DCIS], 43 invasive cancers) and 287 (81.3%) were false-positive. Assessment of MR imaging findings led to a correct diagnosis of no breast cancer in 264 of the 287 false-positive findings (92%) and helped confirm the presence of breast cancer in 63 of 66 malignancies. The false-negative rate for pure clustered microcalcifications was 12% (three of 25 cases) because of three nonenhancing low-grade DCIS cases; in turn, MR imaging depicted additional invasive cancers in three women with false-positive findings from mammography and US. For mammographic findings other than pure clustered microcalcifications, MR imaging increased the positive predictive value (PPV) from 17.5% (21 of 120 cases; 95% confidence interval [CI]: 10.7%, 24.3%) to 78% (21 of 27 cases; 95% CI: 62.1%, 93.5%), with a false-negative rate of 0%. For all US findings, MR imaging increased the PPV from 12.9% (20 of 155 cases; 95% CI: 7.6%, 18.2%) to 69% (20 of 29 cases; 95% CI: 52.2%, 85.8%), again with a false-negative rate of 0%. MR imaging resulted in false-positive findings that led to MR imaging-guided biopsy in five of the 340 patients (1.5%). CONCLUSION: MR imaging is useful for the noninvasive work-up of lesions classified as BI-RADS category 4 at mammography or US and can help avoid 92% of unnecessary biopsies. The false-negative rate was 0% for all US findings and for all mammographic findings except pure clustered microcalcifications. Additional invasive cancers were identified in three women with false-positive findings from mammography and US.

Time-dependent changes of magnetic resonance imaging-visible mesh implants in patients.

OBJECTIVES: Shrinkage and deformation of mesh implants used for hernia treatment can be the cause of long-term complications. The purpose of this study was to quantify noninvasively time-dependent mesh shrinkage, migration, and configuration changes in patients who were surgically treated for inguinal hernia using magnetic resonance imaging (MRI)-visible mesh implants. MATERIALS AND METHODS: In an agarose phantom, meshes in different shrinkage and folding conditions were used to validate the quantification process. Seven patients who were surgically (3 bilaterally) treated for inguinal hernia using iron-loaded mesh implants were prospectively examined using MRI. Gradient echo sequences in sagittal and transverse orientations were performed on day 1 after surgery and at day 90. The mesh-induced signal voids were semiautomatically segmented and a polygonal surface model was generated. A comparison of area and centroid position was performed between the 2 calculated surfaces (day 1 vs day 90). RESULTS: The phantom study revealed a maximum deviation of 3.6% between the MRI-based quantification and the actual mesh size. All 10 implants were successfully reconstructed. The mean (SD) observed mesh shrinkage 90 days after surgery was 20.9% (7.1%). The mean (SD) centroid movement was 1.17 (0.47) cm. Topographic analysis revealed mean (SD) local configuration changes of 0.23 (0.03) cm. CONCLUSIONS: In this study, significant mesh shrinkage (20.9%) but marginal changes in local mesh configuration occurred within 90 days after mesh implantation. Centroid shift of the mesh implant can be traced back to different patient positioning and abdominal distension. The developed algorithm facilitates noninvasive assessment of key figures regarding MRI-visible meshes. Consequently, it might help to improve mesh technology as well as surgical skills.

Target lesion selection: an important factor causing variability of response classification in the Response Evaluation Criteria for Solid Tumors 1.1.

PURPOSE: We conducted a systematic analysis of factors (manual vs automated and unidimensional vs 3-dimensional size assessment, and impact of different target lesion selection) contributing to variability of response categorization in the Response Evaluation Criteria for Solid Tumors 1.1. PATIENTS AND METHODS: A total of 41 female patients (58.1 ± 13.2 years old) with metastatic breast cancer underwent contrast-enhanced thoracoabdominal computed tomography for initial staging and first follow-up after systemic chemotherapy. Data were independently interpreted by 3 radiologists with 5 to 9 years of experience. In addition, response was evaluated by a computer-assisted diagnosis system that allowed automated unidimensional and 3-dimensional assessment of target lesions. RESULTS: Overall, between-reader agreement was moderate (κ = 0.53), with diverging response classification observed in 19 of 41 patients (46%). In 25 patients, readers had chosen the same, and in 16, readers had chosen different target lesions. Selection of the same target lesions was associated with a 76% rate of agreement (19/25) with regard to response classification; selection of different target lesions was associated with an 81% rate of disagreement (13/16) (P < 0.001). After dichotomizing response classes according to their therapeutic implication in progressive versus nonprogressive, disagreement was observed in 11 of 41 patients (27%) (κ = 0.57). In 9 of these 11 patients, readers had chosen different target lesions. Disagreement rates due to manual versus automated or unidimensional versus volumetric size measurements were less important (11/41 and 6/41; 27% and 15%, respectively). CONCLUSIONS: A major source of variability is not the manual or unidimensional measurement, but the variable choice of target lesions between readers. Computer-assisted diagnosis-based analysis or tumor volumetry can help avoid variability due to manual or unidimensional measurements only but will not solve the problem of target lesion selection.

Does MRI breast "density" (degree of background enhancement) correlate with mammographic breast density?

PURPOSE: To investigate whether mammographic breast densities and the respective degree of MRI background enhancement would correlate. Mammographic breast density is coded to communicate how likely a cancer is obscured by parenchyma. Similarly, background enhancement in breast MRI could obscure enhancing cancer tissue. MATERIALS AND METHODS: A total of 468 women underwent standard full-field digital mammography and dynamic contrast-enhanced breast MRI in our institution. Mammographic breast density was scored according to the American College of Radiology-classification; background enhancement in MRI was scored on a 4-point scale from absent to severe. Breast "density classes" were retrospectively compared by analyzing the differences between scores for mammography and MRI. Statistical correlation was calculated using the Spearman coefficient. RESULTS: Scores matched in 19% of women (90/468) but differed in 81% (378/468). A deviation by 1 point was observed in 33% (157/468), by 2 points in 38% (179/468), by 3 in 9% (42/468). Scores for background enhancement were lower than mammographic scores in 371/468 (79.3%), equivalent in 90/468 (19.2%), and higher in 7/468 (1.5%). CONCLUSION: Mammographic breast density does not correlate with the degree of background enhancement in MRI. In the majority of women, scores for background enhancement in MRI will be lower than the respective mammographic density scores.

First in-human magnetic resonance visualization of surgical mesh implants for inguinal hernia treatment.

OBJECTIVES: Until today, there have been no conventional imaging methods available to visualize surgical mesh implants and related complications. In a new approach, we incorporated iron particles into polymer-based implants and visualized them by magnetic resonance imaging (MRI).After clinical approval of such implants, the purposes of this study were to evaluate the MRI conspicuity of such iron-loaded mesh implants in patients treated for inguinal hernias and to assess the immediate postsurgical mesh configuration. MATERIALS AND METHODS: Approved by the ethics committee, in this prospective cohort study, 13 patients (3 patients with bilateral hernia treatment) were surgically treated for inguinal hernia receiving iron-loaded mesh implants between March and October 2012. The implants were applied via laparoscopic technique (transabdominal preperitoneal technique; n = 8, 3 patients with bilateral hernia treatment) or via open surgical procedure (Lichtenstein surgery; n = 5). Magnetic resonance imaging was performed 1 day after the surgery at a 1.5-T scanner (Achieva; Philips, Best, The Netherlands) with a 16-channel receiver coil using 3 different gradient echo sequences (first gradient echo sequence, second gradient echo sequence, and third gradient echo sequence [GRE1-3]) and 1 T2-weighted turbo spin-echo sequence (T2wTSE). Three radiologists independently evaluated mesh conspicuity and diagnostic value with respect to different structures using a semiquantitative scoring system (1, insufficient; 2, sufficient; 3, good; 4, optimal). Mesh deformation and coverage of the hernia were visually assessed and rated using a 5-point semiquantitative scoring system. Statistical analysis was performed using mixed models and linear contrast. RESULTS: All 16 implants were successfully visualized by MRI. On gradient echo sequences, the mesh is clearly delineated as a thick hypointense line. On T2wTSE, the mesh was depicted as a faint hypointense line, which was difficult to identify. The first gradient echo sequence was rated best for visual conspicuity (mean [SD], 3.8 [0.4]). T2-weighted turbo spin-echo sequence was preferred for evaluation of the surrounding anatomy (mean [SD], 3.7 [0.3]). For the combined assessment of both mesh and anatomy, GRE3 was rated best (mean [SD], 2.9 [0.7]). Local air slightly reduced mesh delineation (lowest mean [SD] rating, 2.9 [0.7] for GRE3). Overall, in both implantation techniques, the meshes exhibited mild to moderate deformations (mean [SD], 3.3 [0.4], 3.1 [0.3], and 2.8 [0.3] on average with open technique, 2.7 [0.3], 2.7 [0.2], and 2.3 [0.3] with laparoscopic technique). Coverage of the hernia was achieved in 15 of the 16 implants. CONCLUSIONS: Combining iron-loaded implants and MRI, we achieved mesh visualization for the first time in patients. For MRI protocol, we propose a combination of different gradient echo sequences and T2-weighted turbo spin-echo sequences: first gradient echo sequence for mesh configuration, T2wTSE for anatomy assessment, and GRE3 for evaluation of hernia coverage and mesh localization. Using our approach, MRI could become a noninvasive alternative to open surgical exploration if mesh-related complications were suspected.