Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Adenomyosis in Pregnancy: Diagnostic Pearls and Pitfalls.

Adenomyosis is a common benign uterine disorder in which ectopic endometrial glands extend into the myometrium. Adenomyosis is increasingly diagnosed in young women, affecting 20%-35% of women of reproductive age. Features of adenomyosis can be seen with either US or MRI, especially with newer imaging technology. With advances in reproductive endocrinology as well as a trend toward later maternal age, adenomyosis is increasingly noted during pregnancy, often while performing imaging for other reasons. Hormonal changes during pregnancy alter the appearance of adenomyosis, which includes diffuse, focal, and cystic adenomyosis. Recognizing these imaging changes in pregnancy proves essential for accurately diagnosing adenomyosis as a benign condition, as it mimics serious placental and myometrial abnormalities. Using a lower-frequency US transducer or MRI can be helpful in distinguishing among these entities. Describing the location of adenomyosis in relationship to the site of placentation is also important. Diagnosing adenomyosis is crucial because it can be associated with poor pregnancy outcomes, including spontaneous abortion, preterm birth, and fetal growth restriction. Adenomyosis is also a risk factor for preeclampsia. Intramural ectopic pregnancy is a rare but serious condition that can mimic cystic adenomyosis, and comparison with prepregnancy images can help differentiate the two conditions. The authors review the unique imaging characteristics of adenomyosis in pregnancy, focusing on accurate diagnosis of an underrecognized benign condition that can mimic myometrial and placental pathologic conditions.©RSNA, 2021.

Factors Affecting Image Quality and Lesion Evaluability in Breast Diffusion-weighted MRI: Observations from the ECOG-ACRIN Cancer Research Group Multisite Trial (A6702).

OBJECTIVE: The A6702 multisite trial confirmed that apparent diffusion coefficient (ADC) measures can improve breast MRI accuracy and reduce unnecessary biopsies, but also found that technical issues rendered many lesions non-evaluable on diffusion-weighted imaging (DWI). This secondary analysis investigated factors affecting lesion evaluability and impact on diagnostic performance. METHODS: The A6702 protocol was IRB-approved at 10 institutions; participants provided informed consent. In total, 103 women with 142 MRI-detected breast lesions (BI-RADS assessment category 3, 4, or 5) completed the study. DWI was acquired at 1.5T and 3T using a four b-value, echo-planar imaging sequence. Scans were reviewed for multiple quality factors (artifacts, signal-to-noise, misregistration, and fat suppression); lesions were considered non-evaluable if there was low confidence in ADC measurement. Associations of lesion evaluability with imaging and lesion characteristics were determined. Areas under the receiver operating characteristic curves (AUCs) were compared using bootstrapping. RESULTS: Thirty percent (42/142) of lesions were non-evaluable on DWI; 23% (32/142) with image quality issues, 7% (10/142) with conspicuity and/or localization issues. Misregistration was the only factor associated with non-evaluability (P = 0.001). Smaller (≤10 mm) lesions were more commonly non-evaluable than larger lesions (p <0.03), though not significant after multiplicity correction. The AUC for differentiating benign and malignant lesions increased after excluding non-evaluable lesions, from 0.61 (95% CI: 0.50-0.71) to 0.75 (95% CI: 0.65-0.84). CONCLUSION: Image quality remains a technical challenge in breast DWI, particularly for smaller lesions. Protocol optimization and advanced acquisition and post-processing techniques would help to improve clinical utility.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Discrimination of Malignant and Benign Breast Lesions Using Quantitative Multiparametric MRI: A Preliminary Study.

We aimed to compare diagnostic performance in discriminating malignant and benign breast lesions between two intravoxel incoherent motion (IVIM) analysis methods for diffusion-weighted magnetic resonance imaging (DW-MRI) data and between DW- and dynamic contrast-enhanced (DCE)-MRI, and to determine if combining DW- and DCE-MRI further improves diagnostic accuracy. DW-MRI with 12 b-values and DCE-MRI were performed on 26 patients with 28 suspicious breast lesions before biopsies. The traditional biexponential fitting and a 3-b-value method were used for independent IVIM analysis of the DW-MRI data. Simulations were performed to evaluate errors in IVIM parameter estimations by the two methods across a range of signal-to-noise ratio (SNR). Pharmacokinetic modeling of DCE-MRI data was performed. Conventional radiological MRI reading yielded 86% sensitivity and 21% specificity in breast cancer diagnosis. At the same sensitivity, specificity of individual DCE- and DW-MRI markers improved to 36%-57% and that of combined DCE- or combined DW-MRI markers to 57%-71%, with DCE-MRI markers showing better diagnostic performance. The combination of DCE- and DW-MRI markers further improved specificity to 86%-93% and the improvements in diagnostic accuracy were statistically significant (P < .05) when compared with standard clinical MRI reading and most individual markers. At low breast DW-MRI SNR values (<50), like those typically seen in clinical studies, the 3-b-value approach for IVIM analysis generates markers with smaller errors and with comparable or better diagnostic performances compared with biexponential fitting. This suggests that the 3-b-value method could be an optimal IVIM-MRI method to be combined with DCE-MRI for improved diagnostic accuracy.

Fetal Hepatomegaly: Causes and Associations.

Fetal hepatomegaly is associated with significant fetal morbidity and mortality. However, hepatomegaly might be overlooked when numerous other fetal anomalies are present, or it might not be noticed when it is an isolated entity. As the largest solid organ in the abdomen, the liver can be seen well with US or MRI, and the normal imaging characteristics are well described. The length of the fetal liver, which can be used to identify hepatomegaly, can be determined by measuring the liver from the diaphragm to the tip of the right lobe in the sagittal plane. Fetal hepatomegaly is seen with infection, transient abnormal myelopoiesis, liver storage and deposition diseases, some syndromes, large liver tumors, biliary atresia, and anemia. Some of these diagnoses are treatable during the fetal period. Attention to the associated findings and specific hepatic and nonhepatic imaging characteristics can help facilitate more accurate diagnoses and appropriate patient counseling.©RSNA, 2020.

Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702).

PURPOSE: Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives.Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. RESULTS: Of 107 women enrolled, 67 patients (median age 49, range 24-75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10-3 vs.1.47 × 10-3; P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65-0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10-3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%-31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10-3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers. CONCLUSIONS: DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.

Clinical outcomes following prenatal diagnosis of asymmetric ventriculomegaly, interhemispheric cyst, and callosal dysgenesis (AVID).

OBJECTIVES: When identified prenatally, the imaging triad of asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum (AVID) can indicate a more serious congenital brain anomaly. In this follow-up series of 15 fetuses, we present the neurodevelopmental outcomes of a single institution cohort of children diagnosed prenatally with AVID. METHODS: Our fetal ultrasound database was queried for cases of AVID between 2000 and 2016. All available fetal MR imaging studies were reviewed for the presence of (a) interhemispheric cysts or ventricular diverticula and (b) dysgenesis or agenesis of the corpus callosum. Clinical records were reviewed for perinatal management, postnatal surgical management, and neurodevelopmental outcomes. RESULTS: Fifteen prenatal cases of AVID were identified. Twelve were live-born and three pregnancies were terminated. Of the 12 patients, 11 underwent neurosurgical intervention. Of the eight patients surviving past infancy, seven of eight have moderate to severe neurodevelopmental delays or disabilities, encompassing both motor and language skills, and all have variable visual abnormalities. CONCLUSION: In our cohort of 15 prenatally diagnosed fetuses with AVID, eight survived past infancy and all have neurodevelopmental disabilities, including motor and language deficits, a wide range of visual defects, craniofacial abnormalities, and medical comorbidities.

Diagnostic accuracy and clinical outcomes associated with prenatal diagnosis of fetal absent cavum septi pellucidi.

BACKGROUND: Absence of the cavum septi pellucidi (CSP) on prenatal imaging is historically associated with additional anomalies; however, recent cases of isolated absent CSP have also been identified. This study seeks to assess the accuracy of prenatal imaging in evaluating isolated absent CSP and to describe the spectrum of clinical outcomes. METHODS: This is a retrospective observational study of all prenatally diagnosed absent CSP cases between 2011 and 2016 at our institution. Cases with additional structural parenchymal abnormalities were excluded. Clinical outcomes were abstracted from available records. RESULTS: We identified 15 cases of prenatally diagnosed isolated absent CSP. All patients were initially diagnosed on ultrasound (US) and 11/15 patients had fetal magnetic resonance imaging (MRI) confirming the diagnosis. Prenatal US and MRI were concordant in all cases. Of the continuing pregnancies, 2 neonatal deaths occurred related to extreme prematurity. Two cases of septo-optic dysplasia were identified in our cohort. DISCUSSION: In this study, fetal MRI and US had a high degree of accuracy with concordant postnatal imaging. Our study is similar to other case series suggesting that a range of clinical outcomes is possible with isolated absent CSP, but long-term patient follow up is necessary.

Intrauterine Linear Echogenicities in the Gravid Uterus: What Radiologists Should Know.

Intrauterine linear echogenicity (ILE) is a common ultrasonographic finding in the gravid uterus and has variable causes and variable maternal and fetal outcomes. Correctly categorizing ILE during pregnancy is crucial for guiding surveillance and advanced imaging strategies. Common causes of ILE include membranes in multiple gestations, uterine synechiae with amniotic sheets, and uterine duplication anomalies. Less common causes include circumvallate placenta, chorioamniotic separation, and hemorrhage between membranes. Amniotic band syndrome is a rare but important diagnosis to consider, as it causes severe fetal defects. Imaging findings enable body stalk anomaly, a lethal defect, to be distinguished from amniotic bands, which although destructive are not necessarily lethal. This review describes the key imaging findings used to differentiate the various types of ILE in pregnancy, thus enabling accurate diagnosis and appropriate patient counseling. Online supplemental material is available for this article. ©RSNA, 2018.

Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.

Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10-5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10-5 %ID/g; range, [0.81-4.1] × 10-5 %ID/g) and liver (mean, 0.15 × 10-5 %ID/g; range, [0-0.26] × 10-5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10-5 %ID/g), one juvenile spleen sample (0.039 × 10-5 %ID/g), and one juvenile brain (0.095 × 10-5 %ID/g) and kidney (0.13 × 10-5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.

DCE-MRI Texture Features for Early Prediction of Breast Cancer Therapy Response.

This study investigates the effectiveness of hundreds of texture features extracted from voxel-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parametric maps for early prediction of breast cancer response to neoadjuvant chemotherapy (NAC). In total, 38 patients with breast cancer underwent DCE-MRI before (baseline) and after the first of the 6-8 NAC cycles. Quantitative pharmacokinetic (PK) parameters and semiquantitative metrics were estimated from DCE-MRI time-course data. The residual cancer burden (RCB) index value was computed based on pathological analysis of surgical specimens after NAC completion. In total, 1043 texture features were extracted from each of the 13 parametric maps of quantitative PK or semiquantitative metric, and their capabilities for early prediction of RCB were examined by correlating feature changes between the 2 MRI studies with RCB. There were 1069 pairs of feature-map combinations that showed effectiveness for response prediction with 4 correlation coefficients >0.7. The 3-dimensional gray-level cooccurrence matrix was the most effective feature extraction method for therapy response prediction, and, in general, the statistical features describing texture heterogeneity were the most effective features. Quantitative PK parameters, particularly those estimated with the shutter-speed model, were more likely to generate effective features for prediction response compared with the semiquantitative metrics. The best feature-map pair could predict pathologic complete response with 100% sensitivity and 100% specificity using our cohort. In conclusion, breast tumor heterogeneity in microvasculature as measured by texture features of voxel-based DCE-MRI parametric maps could be a useful biomarker for early prediction of NAC response.

Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI.

The purpose is to compare quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT) and evaluation of residual cancer burden (RCB). Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM). After one NACT cycle the percent changes of DCE-MRI parameters K(trans) (contrast agent plasma/interstitium transfer rate constant), ve (extravascular and extracellular volume fraction), kep (intravasation rate constant), and SSM-unique τi (mean intracellular water lifetime) are good to excellent early predictors of pathologic complete response (pCR) vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT K(trans), τi, and RECIST LD show statistically significant (P < .05) correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy.

Epidemiologic studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2- to 8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ, or invasive ductal carcinoma breast tissues. Within the supplement group, Ki-67 (P = 0.003) and HDAC3 (P = 0.044) levels significantly decreased in benign tissue. Pre-to-postintervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (P = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.

Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate.

PURPOSE: To determine the extent to which gadolinium chelate is found in nonhuman primate fetal tissues and amniotic fluid at 19-45 hours after intravenous injection of a weight-appropriate maternal dose of the contrast agent gadoteridol. MATERIALS AND METHODS: Gravid Japanese macaques (n = 14) were maintained as approved by the institutional animal care and utilization committee. In the 3rd trimester of pregnancy, the macaques were injected with gadoteridol (0.1 mmol per kilogram of maternal weight). Fetuses were delivered by means of cesarean section within 24 hours of maternal injection (range, 19-21 hours; n = 11) or 45 hours after injection (n = 3). Gadolinium chelate levels in the placenta, fetal tissues, and amniotic fluid were obtained by using inductively coupled plasma mass spectrometry. The Wilcoxon rank sum test was used for quantitative comparisons. RESULTS: Gadoteridol was present in the fetoplacental circulation at much lower quantities than in the mother. At both time points, the distribution of gadolinium chelate in the fetus was comparable to that expected in an adult. The highest concentration of the injected dose (ID) was found in the fetal kidney (0.0161% ID per gram in the 19-21-hour group). The majority of the in utero gadolinium chelate was found in the amniotic fluid and the placenta (mean, 0.1361% ID per organ ± 0.076 [standard deviation] and 0.0939% ID per organ ± 0.0494, respectively). Data acquired 45 hours after injection showed a significant decrease in the gadolinium chelate concentration in amniotic fluid compared with that in the 19-21-hour group (from 0.0017% to 0.0007% ID per gram; P = .01). CONCLUSION: Amounts of gadolinium chelate in the fetal tissues and amniotic fluid were minimal compared with the maternal ID. This may impact future clinical studies on the safety of gadolinium contrast agent use in pregnancy.

Using dynamic contrast-enhanced MRI to quantitatively characterize maternal vascular organization in the primate placenta.

PURPOSE: The maternal microvasculature of the primate placenta is organized into 10-20 perfusion domains that are functionally optimized to facilitate nutrient exchange to support fetal growth. This study describes a dynamic contrast-enhanced magnetic resonance imaging method for identifying vascular domains and quantifying maternal blood flow in them. METHODS: A rhesus macaque on the 133rd day of pregnancy (G133, term = 165 days) underwent Doppler ultrasound procedures, dynamic contrast-enhanced magnetic resonance imaging and Cesarean-section delivery. Serial T1 -weighted images acquired throughout intravenous injection of a contrast reagent bolus were analyzed to obtain contrast reagent arrival time maps of the placenta. RESULTS: Watershed segmentation of the arrival time map identified 16 perfusion domains. The number and location of these domains corresponded to anatomical cotyledonary units observed following delivery. Analysis of the contrast reagent wave front through each perfusion domain enabled determination of volumetric flow, which ranged from 9.03 to 44.9 mL/s (25.2 ± 10.3 mL/s). These estimates are supported by Doppler ultrasound results. CONCLUSIONS: The dynamic contrast-enhanced magnetic resonance imaging analysis described here provides quantitative estimates of the number of maternal perfusion domains in a primate placenta and estimates flow within each domain. Anticipated extensions of this technique are to the study placental function in non-human primate models of obstetric complications.

Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

Shutter-speed pharmacokinetic analysis of dynamic-contrast-enhanced (DCE)-MRI data allows evaluation of equilibrium inter-compartmental water interchange kinetics. The process measured here - transcytolemmal water exchange - is characterized by the mean intracellular water molecule lifetime (τi). The τi biomarker is a true intensive property not accessible by any formulation of the tracer pharmacokinetic paradigm, which inherently assumes it is effectively zero when applied to DCE-MRI. We present population-averaged in vivo human breast whole tumor τi changes induced by therapy, along with those of other pharmacokinetic parameters. In responding patients, the DCE parameters change significantly after only one neoadjuvant chemotherapy cycle: while K(trans) (measuring mostly contrast agent (CA) extravasation) and kep (CA intravasation rate constant) decrease, τi increases. However, high-resolution, (1 mm)(2), parametric maps exhibit significant intratumor heterogeneity, which is lost by averaging. A typical 400 ms τi value means a trans-membrane water cycling flux of 10(13) H2O molecules s(-1)/cell for a 12 µm diameter cell. Analyses of intratumor variations (and therapy-induced changes) of τi in combination with concomitant changes of ve (extracellular volume fraction) indicate that the former are dominated by alterations of the equilibrium cell membrane water permeability coefficient, PW, not of cell size. These can be interpreted in light of literature results showing that τi changes are dominated by a PW (active) component that reciprocally reflects the membrane driving P-type ATPase ion pump turnover. For mammalian cells, this is the Na(+), K(+)-ATPase pump. These results promise the potential to discriminate metabolic and microenvironmental states of regions within tumors in vivo, and their changes with therapy.

Asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum (AVID): an imaging triad.

A series of 20 cases from 2 academic institutions is presented with a characteristic imaging triad of asymmetric ventriculomegaly, a large interhemispheric cyst, and partial or complete agenesis of the corpus callosum. Most cases were initially referred as aqueduct stenosis and hydrocephalus or focal porencephaly. We describe the imaging findings that identify an abnormal or absent corpus callosum associated with a type 1 interhemispheric cyst in fetuses initially thought to have hydrocephalus attributable to aqueductal stenosis. We suggest that the acronym AVID (asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum) may be useful in recognition of these cases. All cases presented with markedly asymmetric ventriculomegaly on initial sonography, with progressive hydrocephalus throughout gestation. Fetal magnetic resonance imaging was performed in 15 of 20 cases. Thirteen of 20 cases were identified in male fetuses. Associated fetal and postnatal abnormalities are also reported. Technological improvements in sonography and fetal magnetic resonance imaging allow improved characterization of associated intracranial anomalies in the setting of hydrocephalus. Accurate diagnosis can aid parental counseling, especially because isolated aqueductal stenosis suggests a better prognosis than hydrocephalus with anomalies. Markedly asymmetric ventriculomegaly in this series was the key to excluding isolated aqueductal stenosis and was associated with callosal malformation with a type 1a interhemispheric cyst.