Percentage Enhancement Research Articles

Abstract PO5-07-07: The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk

Abstract Introduction: The amount and degree of the fibroglandular tissue (FGT) enhancement on breast MRI, known as background parenchymal enhancement (BPE), is an emerging marker of breast cancer risk. Higher qualitative and quantitative BPE levels have been shown to correlate with both future risk of initial breast cancer diagnosis and breast cancer recurrence after treatment. Furthermore, adjuvant and preventative therapies such as radiation and endocrine therapy have been shown to lower BPE in many women, potentially serving as a marker of treatment efficacy. However, the biological basis of BPE remains unclear and elucidation of this mechanism could identify novel targeted prevention strategies. The goal of this study was to assess the association of BPE levels with markers of inflammation, vascularity, proliferation, and estrogen sensitivity in a cohort of high-risk women. Materials and Methods: In this IRB-approved retrospective study, we identified asymptomatic high-risk women who underwent at least one dynamic contrast-enhanced (DCE) breast MRI within one year of prophylactic bilateral mastectomy. Qualitative BPE assessments were obtained from clinical reports. Quantitative BPE measures were obtained using in-house semi-automated software: whole breast FGT was first segmented on pre-contrast images, percent enhancement (PE) was calculated for each voxel as (S1-S0)/S0 × 100%, where S0 and S1 are pre- and early post-contrast signal intensity, respectively, and quantitative BPE was then defined as the mean PE of the FGT. Additionally, the BPE volume ratio was calculated as the fraction of FGT that had a PE >50%. Histopathology markers of inflammation (COX-2), vascularity (VEGF), proliferation (Ki-67), and estrogen receptor status (ER) were prospectively measured on archived mastectomy specimens of each breast. BPE metrics were correlated with histopathological markers using Spearman’s rank correlation, with and without adjustment by menopausal status of the patient. All tests were based on generalized estimating equations models to account for the non-independence of the two breasts per patient. A p-value < 0.05 was considered significant. Results: We identified 56 women (median age: 39; range: 26-63 years) for this study, of which 39% were post-menopausal (N=22). Distribution of qualitative BPE levels were 41% minimal (N=23), 29% mild (N=16), 18% moderate (N=10), and 12% marked (N=7). Qualitative BPE and quantitative BPE markers were moderately positively correlated (r=0.37-0.54, p< 0.01). Table 1 lists the correlations between BPE metrics and histopathology markers. After adjusting for menopausal status, qualitative BPE was positively associated with ER (r=0.27, p=0.02) and VEGF (r=0.24, p< 0.01; r=0.21, p=0.02 adjusted). Quantitative BPE and BPE volume ratio were both positively correlated with VEGF (p< 0.04) and negatively correlated with COX2 (p< 0.05). No significant associations were observed between BPE and Ki-67. Discussion: Our study suggests that increased BPE on MRI positively correlates with increased vascularity and higher estrogen receptor expression but not inflammation or proliferation within normal breast tissue in high-risk women. These findings, along with established associations between BPE and cancer risk, could be useful to select and assess efficacy of targeted preventative treatments. Table. Spearman rank correlations between BPE metrics and histopathological markers. Citation Format: Pegah Khoshpouri, Anum Kazerouni, Sana Parsian, Daniel Hippe, Olivia Walsh, Lisa Koch, Savannah Partridge, Habib Rahbar. The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-07.

Abstract PO4-07-06: Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study

Abstract Purpose: The aim of this study was to develop a radiomics nomogram using breast MRI data and preoperative pathologic information to predict oncotype DX recurrence score (RS) in patients with estrogen receptor-positive early-stage breast cancer (EBC). Materials and methods: In this retrospective study, a total of 493 patients with EBC, diagnosed through core needle biopsy and who underwent preoperative breast MRI at a single institution between 2011 and 2017, were included. The patients were categorized based on RS, age at surgery, and nodal status, as suggested by the TAILORX trial, and out of the included patients, 249 were identified as likely to benefit from chemotherapy, while 244 were deemed safe to forgo chemotherapy. Radiomic features were extracted from three-dimensional segmentations of each tumor, and computer-extracted image phenotypes (CEIP) were generated from early post-contrast T1-weighted images, percent enhancement (PE) maps, and signal enhancement ratio (SER) maps. The patient cohort was divided into a training set (n=329) and a validation set (n=164). Feature selection and radiomics score construction were performed using elastic net, and a prediction model was developed using multivariate logistic regression analysis. The radiomics score, along with independent pathologic risk factors, was incorporated into a radiomics nomogram. Internal validation was conducted using an independent validation set (n=164). Results: The radiomics score, composed of 24 selected CEIPs, demonstrated a significant association with recurrence prediction (C-index, 0.769 for training set and 0.745 for validation set). The independent pathologic predictors included in the nomogram were histology, estrogen receptor status, progesterone receptor status, nuclear grade, histologic grade, HER1, CK56, P53, and Ki67 status, with a C-index of 0.858 for the training set and 0.774 for the validation set. Adding the radiomics score to the pathologic nomogram resulted in incremental values of 0.054 and 0.092, respectively. The radiomics nomogram showed favorable prediction of low-risk RS, with a C-index of 0.912 for the training set and 0.866 for the validation set. Conclusion: This study demonstrated that an MRI-based radiomics nomogram incorporating the radiomics score and preoperatively obtained pathologic data can effectively predict oncotype DX RS and the benefit of adjuvant chemotherapy in EBC patients. The model improves risk assessment availability and timeliness for patients with EBC. Citation Format: Minji Song, Hee Jung Shin. Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-06.

Quantitative assessment of background parenchymal enhancement is associated with lifetime breast cancer risk in screening MRI

ObjectivesTo compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI.Materials and methodsThis study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann–Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values.ResultsAge, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PEFGT (11.5 vs. 8.0%, adjusted p = 0.018) and SERFGT (7.2 vs. 9.3%, adjusted p = 0.066).ConclusionQuantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE.Clinical relevance statementBRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models.Key PointsExpanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols.Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers.This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations.

18F-FDG Dedicated Breast PET Complementary to Breast MRI for Evaluating Early Response to Neoadjuvant Chemotherapy.

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 (18F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and 18F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points. Differences between FDG dbPET and MRI parameters were evaluated after stratifying by receptor status, Ki-67 index, and residual cancer burden. Parameters were compared using Wilcoxon signed rank and Mann-Whitney U tests. Results High Ki-67 tumors had higher baseline SUVmean (difference, 5.1; P = .01) and SUVpeak (difference, 5.5; P = .04). At T1, decreases were observed in FDG dbPET measures (pseudo-median difference T0 minus T1 value [95% CI]) of SUVmax (-6.2 [-10.2, -2.6]; P < .001), SUVmean (-2.6 [-4.9, -1.3]; P < .001), SUVpeak (-4.2 [-6.9, -2.3]; P < .001), and TLG (-29.1 mL3 [-71.4, -6.8]; P = .005) and MRI measures of SERpeak (-1.0 [-1.3, -0.2]; P = .02) and FTV (-11.6 mL3 [-22.2, -1.7]; P = .009). Relative to nonresponsive tumors, responsive tumors showed a difference (95% CI) in percent change in SUVmax of -34.3% (-55.9%, 1.5%; P = .06) and in PEpeak of -42.4% (95% CI: -110.5%, 8.5%; P = .08). Conclusion 18F-FDG dbPET was sensitive to early changes during NAC and provided complementary information to DCE MRI that may be useful for treatment response evaluation. Keywords: Breast, PET, Dynamic Contrast-enhanced MRI Clinical trial registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2024.

Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Abstract PD11-08: Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer

Abstract Introduction: In triple-negative breast cancer (TNBC), both response to neoadjuvant chemotherapy (NAC) and the degree of pre-treatment (pre-tx) tumor immune infiltration as defined by tumor-infiltrating lymphocytes (TILs) are prognostic. Improving NAC response prediction in early TNBC would provide the opportunity to consider adjustments to the NAC regimen prior to initiating therapy. Breast magnetic resonance imaging (MRI) enables noninvasive whole-tumor measurement of microenvironment features. We investigated the value of pre-tx MRI metrics in addition to TILs for the prediction of NAC response in early TNBC patients. Methods: Women with Stage I-III TNBC who underwent pre-tx clinical breast MRI and NAC at our institution (2005-2019) were retrospectively identified. Response to NAC was noted, with pathologic complete response (pCR) defined as no residual invasive cancer present within the breast. When tissue was available, diagnostic biopsy was used to quantify pre-tx TILs as deciles from 10-100% by a breast pathologist. Patients underwent pre-tx breast MRI on either a 1.5T or 3T scanner including diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) MRI. From DCE-MRI, tumor longest diameter (LD) and T stage (1-4), as well as contrast kinetics including percent enhancement (PE) at 2 minutes post-contrast and signal enhancement ratio (SER) were determined. Tumor peak PE and peak SER (representing the highest mean PE and SER, respectively, for 3×3 voxel subregions) and functional tumor volume (FTV, tumor volume exhibiting PE ≥ 50%) were calculated. Mean apparent diffusion coefficient (ADC) was calculated from DW-MRI. TIL levels and imaging features were compared between pCR and non-pCR groups by Wilcoxon rank sum test and performance for prediction of pCR was evaluated using areas under the curve (AUC) measures from receiver operating characteristic curve analysis. Results: 115 TNBC patients (median age: 49, range 26-79 years) were evaluated, of which 45 (39%) achieved pCR. The majority received an anthracycline-containing regimen. Pre-tx TILs (evaluated in N=60 with available biopsy specimens) ranged from 10% to 80% (median, 10%) and were significantly higher in pCR vs. non-pCR patients (p = 0.02, AUC = 0.63). Pre-tx lesion size on imaging was predictive of response (Table 1), with pCR patients having significantly lower LD (p &amp;lt; 0.01, AUC = 0.68) and FTV (p = 0.01, AUC = 0.67). Peak PE was also associated with response, significantly lower in pCR patients (p = 0.04, AUC = 0.62), while SER and ADC were not (p &amp;gt; 0.05). Stratifying by T stage, both peak PE (p = 0.03) and FTV (p = 0.05) were predictive of response in T1/T2 patients, while no imaging metrics reached significance in T3/T4 patients. Discussion: In a large cohort of TNBC patients undergoing NAC, measures of tumor size and immune infiltration were strongly predictive of NAC response. Preliminary results suggest that baseline peak PE and FTV are associated with NAC response, particularly in earlier stage TNBC patients. These findings support the utility of imaging and TILs assessments to predict response in TNBC and potentially guide NAC regimens for improved outcomes. Future work will extend these analyses to assess the value of changes in imaging metrics over the course of NAC to predict response. Acknowledgments: NIH P30CA015704, R01CA248192, and Roger E. Moe Fellowship, ASCO/CCF Hayden Family Foundation Young Investigator Award in Breast Cancer Summary of imaging characteristics across TNBC cohort. Values indicate mean (standard deviation).Whole cohort. N=115T1/T2. N=80T3/T4. N=35pCR. N=45non-pCR. N=70pAUCpCR. N=39non-pCR. N=41pAUCpCR. N=6non-pCR. N=29pAUCLongest dimension (mm)34 (15)50 (27)&amp;lt;0.010.6829 (11)31 (10)0.410.5561 (6)76 (20)0.060.75FTV (cm3)14.7 (17.0)31.2 (43.4)0.010.6710.4 (11.0)19.0 (20.2)0.050.6446.1 (24.5)52.0 (58.0)0.720.57Peak SER1.77 (0.26)1.78 (0.23)0.960.501.76 (0.26)1.79 (0.23)0.690.531.91 (0.19)1.78 (0.26)0.270.68Peak PE (%)234 (61)268 (69)0.040.62237 (61)275 (71)0.030.66247 (70)256 (63)1.000.5ADC(×10-3 mm2/s)1.19 (0.29)1.31 (0.36)0.180.581.16 (0.28)1.24 (0.30)0.390.561.40 (0.30)1.4 (0.43)0.900.48 Citation Format: Anum S Kazerouni, Laura C. Kennedy, Michael Hirano, Bonny Chau, Debosmita Biswas, Shaveta Vinayak, Matthew J. Nyflot, Habib Rahbar, Suzanne Dintzis, Savannah C. Partridge. Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-08.

Abstract PS13-50: Relationship of dedicated breast PET and MRI features in breast cancer patients receiving neoadjuvant chemotherapy

Abstract Introduction: Dedicated breast positron emission tomography (dbPET) is an emerging imaging technique with the spatial resolution needed to assess functionality and intra-tumor heterogeneity in primary breast lesions. Breast cancer patients may benefit from dbPET imaging combined with molecularly targeted agents to non-invasively assess and predict response to targeted therapy in the neoadjuvant treatment setting. We have previously observed that [18F]-fluorodeoxyglucose (FDG) PET provides tumor metabolic information complementary to the angiogenic properties reflected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for characterizing triple-negative breast cancers (TNBC) (1). In this study, we examined the relationship between FDG-dbPET and MRI features in a cohort of breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods: With institutional review board approval, patients with biopsy-proven locally-advanced breast cancer were imaged with breast MRI and dbPET before (T0) and after three weeks (T1) of NAC. Standard DCE-MRI was obtained using a dedicated breast coil. Patients also underwent dbPET with 5 mCi of FDG at 45 minutes post-injection. Functional tumor volumes (FTV) were calculated from DCE-MRI by summing all voxels with an early percent enhancement (PE) exceeding 70% within a manually defined volume of interest (VOI). Maximum and mean PE (PEMax, PEMean) values within the VOI were also computed for analyses. Tumors were segmented in dbPET images using semi-automated threshold-driven methods. Body weight-corrected maximum and mean standardized uptake values (SUVMax, SUVMean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were calculated for FDG-dbPET. Percent change relative to T0 (Δ = 100*(T1 - T0)/T0) was calculated for each feature. Spearman’s correlation coefficient was used to evaluate the relationship between MRI and dbPET features. Results: Of the 16 patients enrolled in this study, 13 patients (N = 15 unique tumors) with MRI and dbPET at T0 and T1 were included in the analysis. 46% (6/13) of the patients had TNBC. Our initial findings indicated that ΔPEMax and ΔSUVMax had the highest correlation (ρ = 0.59, p = 0.022). FTV and TLG at T1 were also correlated (ρ = 0.56, p = 0.032). Among all imaging features, ΔMTV showed the largest post-treatment difference between TNBC (-54.5%) and non-TNBC (-6.06%) groups. Among MRI features, ΔFTV exhibited the largest difference between the groups: -70.4% in TNBC and -43.1% in non-TNBC. ΔSUVMax and ΔTLG were additional dbPET features with large differences between TNBC and non-TNBC patients (Table 1). Conclusion: This exploratory study suggests that post-treatment ΔSUVMax and TLG provide complementary metabolic information to angiogenic properties (ΔPEMax and FTV, respectively) reflected by MRI. Other dbPET features may provide independent information adjunct to MRI for describing primary breast tumors. Patients with TNBC exhibited larger reductions in FDG uptake values and metabolic volume than non-TNBC patients. These observed reductions may improve early treatment response in patients with TNBC, enabling more precise treatment guidance. Further studies in larger cohorts are needed to validate these initial observations. 1. Bolouri MS, et al. Triple-Negative and Non-Triple-Negative Invasive Breast Cancer: Association between MR and Fluorine 18 Fluorodeoxyglucose PET Imaging. Radiology 2013;269:354-61 Comparison of ΔMRI and ΔFDG-dbPET in TNBC vs non-TNBC patientsAll Tumors (N = 15 tumors) Median(IQR)TNBC (N = 6 tumors) Median(IQR)non-TNBC (N = 9 tumors) Median(IQR)DCE-MRIΔFTV (%)-66.1 (-77.6, -19.1)-70.4 (-79.0, -62.1)-43.1 (-72.5, -2.95)ΔPEMax (%)-9.91 (-31.5, 19.5)-10.3 (-26.3, 24.2)-9.91 (-31.8, 8.42)ΔPEMean (%)-10.7 (-22.4, 2.77)-9.57 (-12.8, 0.29)-17.0 (-26.0, 2.33)FDG-dbPETΔSUVMax (%)-31.6 (-53.9, -20.6)-47.3 (-55.7, -41.1)-23.1 (-31.6, 1.13)ΔSUVMean (%)-34.1 (-65.4, -14.2)-48.5 (-74.6, -9.74)-34.1 (-44.5, -14.8)ΔMTV (%)-6.18 (-57.0, 38.5)-54.5 (-75.4, 15.3)-6.06 (-47.2, 38.9)ΔTLG (%)-64.9 (-75.2, 23.3)-75.2 (-84.0, -60.0)-47.9 (-65.2, 31.1) Citation Format: Deep K Hathi, Ella F Jones, Wen Li, David C Newitt, Ruby Guo, Youngho Seo, Robert R Flavell, Bonnie N Joe, Diane Heditsian, Susie Brain, ISPY-2 Imaging Working Group, ISPY-2 Consortium, Laura J Esserman, Nola M Hylton. Relationship of dedicated breast PET and MRI features in breast cancer patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-50.

The combined use of EphA2/MMP-2 expression and MRI findings contributes to the determination of cerebral glioma grade.

Glioma is the most aggressive brain tumor and is associated with a high mortality rate. The aim of the present study was to explore the association between matrix metalloproteinase 2 (MMP-2) and ephrin type-A receptor 2 (EphA2) expression in glioma cells, and to investigate the contribution of magnetic resonance imaging (MRI) in glioma classification. A total of 43 patients with pathologically confirmed glioma were divided into two groups as follows: Low-grade (grades I and II; n=21) and high-grade (grades IV and IV; n=22). Subsequently, immunohistochemistry staining was performed to detect the expression levels of MMP-2 and EphA2 in the low- and high-grade groups. MRI routine and enhanced scans were used to measure the peritumoral edema index (EI), tumor enhancement percentage (EP) and maximum tumor diameter. The results demonstrated that the proportion of MMP-2-positive patients in the high-grade group was 86.36% (19/22), which was significantly higher than that of the low-grade group (57.14%; 12/21) (P<0.05). Furthermore, the proportion of EphA2-positive patients in the high-grade group was 90.91% (20/22), significantly higher than that in the low-grade group (4.76%; 1/21) (P<0.01). In addition, the MRI results indicated that the EI, EP and maximum tumor diameter were significantly higher in the high-grade group compared with the low-grade group (P<0.01, P<0.01 and P<0.05, respectively). Finally, the expression levels of MMP-2 and EphA2 were significantly associated with the EI, EP and maximum tumor diameter (all P<0.05). In conclusion, the expression levels of MMP-2 and EphA2 were positively correlated with glioma invasion. The correlation between these expression levels and MRI assessment of the EI, EP and maximum tumor diameter indicated that the combination of these two methods may be used for the evaluation of the tumor grade and for further clinical treatment applications.

Contrast Enhancement in Breast Cancer and Background Mammary-Gland Tissue During the Super-Early Phase of Dynamic Breast Magnetic Resonance Imaging

We aimed to compare the contrast enhancement between tumor and mammary-gland tissue to distinguish lesions in the super-early phase, during which minimal contrast media uptake is observed in mammary-gland tissue. Dynamic magnetic resonance imaging, including the super-early phase with bolus tracking (BT) method (to determine the optimal imaging start time), was performed by using identical parameters to obtain transverse fat-suppressed T1-weighted images of both breasts. The percent enhancement (PE) and the contrast ratio (CR) indicators for tumor and mammary-gland tissue were assessed in each dynamic phase. The PE values of the tumor were 62.4% and 151.6%, and those of the mammary gland were 0.3% and 20.7% in the super-early and early phases, respectively. Therefore, virtually no background parenchymal enhancement was observed in the super-early phase. The variation in the PE values during the super-early phase was significantly smaller when the values were determined with the BT method (P < .05). The CR was highest in the early phase, and the CR in the super-early phase was lower than in the other phases. Early-phase PE and CR were significantly higher in invasive cancer cases than in noninvasive cancer cases (P < .01). A significant difference in the imaging start time was observed for the anatomic side factor by the BT method. Background parenchymal enhancement almost never appeared in the super-early phase, but the CR was lower in the super-early phase than in the early phase. The BT method allowed for an optimal imaging start time for the super-early phase and yielded images with less deviation of contrast enhancement.

Effect of Imaging Parameter Thresholds on MRI Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes.

The purpose of this study is to evaluate the predictive performance of magnetic resonance imaging (MRI) markers in breast cancer patients by subtype. Sixty-four patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy were enrolled in this study. Each patient received a dynamic contrast-enhanced (DCE-MRI) at baseline, after 1 cycle of chemotherapy and before surgery. Functional tumor volume (FTV), the imaging marker measured by DCE-MRI, was computed at various thresholds of percent enhancement (PEt) and signal-enhancement ratio (SERt). Final FTV before surgery and percent changes of FTVs at the early and final treatment time points were used to predict patients’ recurrence-free survival. The full cohort and each subtype defined by the status of hormone receptor and human epidermal growth factor receptor 2 (HR+/HER2-, HER2+, triple negative) were analyzed. Predictions were evaluated using the Cox proportional hazard model when PEt changed from 30% to 200% in steps of 10% and SERt changed from 0 to 2 in steps of 0.2. Predictions with high hazard ratios and low p-values were considered as strong. Different profiles of FTV as predictors for recurrence-free survival were observed in each breast cancer subtype and strong associations with survival were observed at different PEt/SERt combinations that resulted in different FTVs. Findings from this retrospective study suggest that the predictive performance of imaging markers based on FTV may be improved with enhancement thresholds being optimized separately for clinically-relevant subtypes defined by HR and HER2 receptor expression.

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

ObjectiveTo determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer. Methods and materialsOur institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADCmean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS. ResultsMedian follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADCmean, SUVmax, MTV and TLG according to FIGO stage (p<0.001–0.025). There were significant correlations between ADCmean, MTV, TLG and LN metastasis (p=0.017–0.032). SUVmax was not associated with LN metastasis. FIGO stage (p=0.017/0.033), LN metastases (p=0.001/0.020), ADCmean (p=0.007/0.020) and MTV (p=0.014/0.026) were adverse predictors of both DFS/OS. maxTD (p=0.005) and TLG (p=0.024) were adverse predictors of DFS. PE and SUVmax did not correlate with DFS or OS (p=0.18–0.72). ConclusionsQuantitative parameters derived from pre-treatment DW-MRI (ADCmean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.

MRI enhancement in stromal tissue surrounding breast tumors: association with recurrence free survival following neoadjuvant chemotherapy.

Rationale and ObjectivesNormal-appearing stromal tissues surrounding breast tumors can harbor abnormalities that lead to increased risk of local recurrence. The objective of this study was to develop a new imaging methodology to characterize the signal patterns of stromal tissue and to investigate their association with recurrence-free survival following neoadjuvant chemotherapy.Materials and MethodsFifty patients with locally-advanced breast cancer were imaged with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before (V1) and after one cycle (V2) of adriamycin-cytoxan therapy. Contrast enhancement in normal-appearing stroma around the tumor was characterized by the mean percent enhancement (PE) and mean signal enhancement ratio (SER) in distance bands of 5 mm from the tumor edge. Global PE and SER were calculated by averaging all stromal bands 5 to 40 mm from tumor. Proximity-dependent PE and SER were analyzed using a linear mixed effects model and Cox proportional hazards model for recurrence-free survival.ResultsThe mixed effects model displayed a decreasing radial trend in PE at both V1 and V2. An increasing trend was less pronounced in SER. Survival analysis showed that the hazard ratio estimates for each unit decrease in global SER was statistically significant at V1 [estimated hazard ratio = 0.058, 95% Wald CI (0.003, 1.01), likelihood ratio p = 0.03]; but was not so for V2.ConclusionsThese findings show that stromal tissue outside the tumor can be quantitatively characterized by DCE-MRI, and suggest that stromal enhancement measurements may be further developed for use as a potential predictor of recurrence/disease-free survival following therapy.

Enhancement of Ovarian Malignancy on Clinical Contrast Enhanced MRI Studies

Purpose. To assess if there is a significant difference in enhancement of high grade serous carcinoma of the ovary compared with other ovarian malignancies on clinically performed contrast enhanced MRI studies. Methods. In this institutional-review–board-approved study, two radiologists reviewed contrast enhanced MRI scans in 37 patients with ovarian cancer. Readers measured the signal intensity (SI) of ovarian mass and gluteal fat pre- and postcontrast administration. Percentage enhancement (PE) was calculated as [(post-pre)/precontrast SI] × 100. Results. Pathology revealed 19 patients with unilateral and 18 patients with bilateral malignancies for a total of 55 malignant ovaries-high grade serous carcinoma in 25/55 ovaries (45%), other epithelial carcinomas in 12 ovaries (22%), nonepithelial cancers in 8 ovaries (14%), and borderline tumors in 10 ovaries (18%). Enhancement of high grade serous carcinoma was not significantly different from other invasive ovarian malignancies (Reader 1 P = 0.865; Reader 2 P = 0.353). Enhancement of invasive ovarian malignancies was more than borderline tumors but did not reach statistical significance (Reader 1P = 0.102; Reader 2 P = 0.072). Conclusion. On clinically performed contrast enhanced MRI studies, enhancement of high grade serous ovarian carcinoma is not significantly different from other ovarian malignancies.

Optimization of the dynamic, Gd-EOB-DTPA-enhanced MRI of the liver: the effect of the injection rate

Tissue-specific gadolinium-based contrast agents such as Gd-BOPTA, Gd-EOB-DTPA are increasingly used for liver imaging. Despite the added value of the hepatobiliary phase a proper arterial phase is still critical, especially in patients with chronic liver diseases. So far, there are limited data in the literature about the effect of the injection speed of Gd-EOB-DTPA in liver and vessel enhancement. To evaluate the effect of injection rate on the enhancement of liver parenchyma and vasculature in Gd-EOB-DTPA-enhanced liver MRI. Eighty patients who underwent Gd-EOB-DTPA-enhanced liver MRI (1.5T multi-channel MR-system) were retrospectively evaluated. We used a Care Bolus technique with an injection rate of 2 mL/s in group 1 (n = 40) and a Care Bolus technique with an injection rate of 1 mL/s in group 2 (n = 40) to determine the start of the arterial-dominant phase. Signal intensities were measured in vascular structures and liver parenchyma. Signal-to-noise-ratio (SNR), SNR increase (SNRi), and percentage enhancement (PE) were calculated and compared by a students t-test. The SNR, SNRi, and PE of the aorta in the arterial phase were significantly higher in group 2 in comparison to group 1 (P = 0.007, P = 0.0043, and P < 0.001, respectively). There were no significant differences concerning the SNR, SNRi, or PE of the portal vein and the normal liver parenchyma between both groups at all time points. The study shows that a lower injection rate of 1 mL/s enables a higher enhancement in the aorta in the arterial phase compared with Gd-EOB-DTPA-enhanced MRI with the more commonly used injection rate of 2 mL/s.

Different signal intensity at Gd‐EOB‐DTPA compared with Gd‐DTPA‐enhanced MRI in hepatocellular carcinoma transgenic mouse model in delayed phase hepatobiliary imaging

To evaluate hyperintense Gd-DTPA- compared with hyper- and hypointense Gd-EOB-DTPA-enhanced magnet resonance imaging (MRI) in c-myc/TGFα transgenic mice for detecting hepatocellular carcinoma (HCC). Twenty HCC-bearing transgenic mice with overexpression of the protooncogene c-myc and transforming growth factor-alpha (TGF-α) were analyzed. MRI was performed using a 3-T MRI scanner and an MRI coil. The imaging protocol included Gd-DTPA- and Gd-EOB-DTPA-enhanced T1-weighted images. The statistically evaluated parameters are signal intensity (SI), signal intensity ratio (SIR), contrast-to-noise ratio (CNR), percentage enhancement (PE), and signal-to-noise ratio (SNR). On Gd-DTPA-enhanced MRI compared with Gd-EOB-DTPA-enhanced MRI, the SI of liver was 265.02 to 573.02 and of HCC 350.84 to either hyperintense with 757.1 or hypointense with 372.55 enhancement. Evaluated parameters were SNR of HCC 50.1 to 56.5/111.5 and SNR of liver parenchyma 37.8 to 85.8, SIR 1.32 to 1.31/0.64, CNR 12.2 to 26.1/-30.08 and PE 42.08% to 80.5/-98.2%, (P < 0.05). Gd-EOB-DTPA is superior to Gd-DTPA for detecting HCC in contrast agent-enhanced MRI in the c-myc/TGFα transgenic mouse model and there was no difference between the hyperintense or hypointense appearance of HCC. Either way, HCCs can easily be distinguished from liver parenchyma in mice.

Expression of VEGF and MMP-9 and MRI imaging changes in cerebral glioma

The purpose of the present study was to investigate the association of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) expression with the histopathological grading of tumors in cerebral glioma. A total of 45 patients with pathologically confirmed cerebral glioma were divided into two groups: a low-grade group (grades I and II, 21 cases) and a high-grade group (grades III and IV, 24 cases). Immunohistochemical staining of tumor samples showed the percentages of tumors expressing VEGF and MMP-9 in the high-grade group to be 95.83 and 75%, respectively, significantly higher than those of the low-grade group (66.67 and 23.81%, P<0.05 and P<0.01, respectively). The magnetic resonance imaging (MRI) results indicated that the peripheral edema index (EI), enhancement percentage (EP), and the maximum diameter of the tumor in the high-grade group were significantly higher than those in the low-grade group (P<0.05, P<0.01, and P<0.05). Moreover, the expression of VEGF and MMP-9 was positively correlated with EI, EP and the maximum diameter of the tumor (P<0.05). Therefore, VEGF and MMP-9 expression were correlated to the invasion of glioma. The association of their expression levels with EI, EP and the maximum tumor diameter indicates that these markers may be used to estimate tumor malignancy for future clinical diagnosis and treatment.

MR quantification of abnormal stromal enhancement in the periphery of invasive breast tumors

636 Background: In dynamic contrast-enhanced MRI (DCEMRI), properties of tissue microvasculature and overall vascularity can be quantified using kinetics of contrast enhancement. It has been shown that areas with high signal enhancement ratio (SER) were significantly correlated with high tumor vascularity, and that mean SER in nearby non-cancerous breast stroma was significantly associated with disease free survival. No universally accepted methods exist to determine the optimal extent of histologically normal breast tissue to treat. Although a relationship between normal tissue SER and recurrence has been observed, the spatial relationship of enhancement within the non-cancerous stroma with respect to proximity of the tumor has not been shown. We hypothesized that abnormalities in vasculature exist within the histologically normal breast stroma that can be detected by measuring changes in enhancement intensity. Methods: We performed a secondary analysis of pre-treatment DCEMRI data from 27 invasive breast cancer patients. An automated, user-independent program was used to segment breast tissue from all other structures. A SER threshold was set to identify invasive tumor regions, and a tumor proximity map was generated giving the 3D distance of each normal breast tissue voxel to the nearest tumor voxel. A percent enhancement (PE) map was calculated for the normal stroma using the signal intensity change between the pre-contrast and post-contrast images. The proximity and PE maps were then combined to measure breast tissue enhancement at various distances from the tumor. Results: PE levels in normal breast tissue situated within 2 cm of the tumor region were significantly higher than at all more distant regions. Pairwise comparisons with Turkey's adjusted p-values indicated that the mean PE at 0 cm-1 cm is significantly higher than all other distant levels (p = &lt; 0.0001) and the mean PE at 1 cm-2 cm is significantly higher than 5 cm-6 cm (p = 0.006). Conclusions: Here, we show that the normal-appearing breast stroma within 0 cm to 2 cm of a primary tumor exhibits higher enhancement levels than stroma located far from the tumor. These results suggest that tissue surrounding the tumor region may contain tumor-related angiogenesis. These findings could help personalize surgery and radiation techniques. No significant financial relationships to disclose.

Tissue characterization of myocardial infarction using T1ρ: Influence of contrast dose and time of imaging after contrast administration

To determine whether contrast between acutely infarcted and normal myocardia in T1-rho-weighted cine TFE (T1rho-TFE) and delayed-enhancement (DE) images (measured using a metric percent enhancement (PE)) varied with the dose or time of imaging after contrast administration. Eighteen patients with acute myocardial infarction (AMI) were randomly divided into three groups according to the dose of gadoversetamide (0.1, 0.2, or 0.3 mmol/kg) administered. After contrast administration, T1rho-TFE images were acquired at five and 40 minutes, and DE images were acquired at 10 and 30 minutes. For T1rho-TFE imaging the PE values at 40 minutes were 70+/-14, 98+/-14, and 105+/-41 at 0.1, 0.2, and 0.3 mmol/kg dose levels, which were significantly greater than the corresponding PEs at five minutes after contrast administration (44+/-12, 71+/-14, and 36+/-13). For DE and T1rho-TFE imaging the dose of contrast agent did not significantly affect the PE. However, with DE the PE tended to increase with the dose. At all dose levels, irreversible injury was more conspicuous in T1rho-TFE images acquired at 40 minutes than at five minutes after contrast. In T1rho-TFE, acute infarction was more conspicuous in images acquired at a later time point, and the PE did not vary with the contrast dose.

MR imaging findings in transient osteoporosis of the hip

Purpose: The authors sought to describe the magnetic resonance (MR) imaging findings including perfusion imaging, in association with the course of acute bone marrow oedema syndrome (aBMEs), in a group of patients with acute hip pain and a final diagnosis of transient osteoporosis of the hip (TOH). Materials and methods: From 217 patients referred with a probable diagnosis of avascular necrosis (AVN) of the femoral head, we identified 42 patients who had clinical and radiographic findings not relevant to AVN. MR imaging examinations were performed on a 1.0T scanner. Perfusion imaging was performed in 20 patients. The bone marrow oedema (BME) was classified in four stages. In addition, the presence or absence of oedema in the subchondral area and the presence of other subchondral lesions were recorded. Acetabular bone marrow was also assessed for the presence of oedema. The quantitative measurements included: maximum size of the effusion, percentage of enhancement (PE) and time of peak enhancement of abnormal marrow compared to the first pass, on the perfusion images. Results: Osteopenia was present on plain radiographs in 87% of cases. The most common pattern of BME was extending to the femoral head and neck. Acetabulum was involved in 16.6%. In 22.6% the BME spared the subchondral region of the femoral head. There were two cases (4.7%) with subchondral changes. A joint effusion was noted in 33 of the 42 patients. On perfusion imaging, a delayed peak enhancement was noted in 20 patients between 40 and 65 s after the first pass of contrast. No patient had any evidence of femoral head collapse or change in sphericity on follow-up MRI. None of the patients developed avascular necrosis in a time frame of 18 months from the onset of the acute hip pain. Conclusion: The aBMEs MR imaging pattern varies and is most commonly appearing on X-rays as osteopenia. Absence of subcondral lesions, delayed peak enhancement of the abnormal marrow on perfusion images, and sparing of subchondral zone from marrow oedema are MR imaging findings highly correlated to TOH.