Leveraging Radiopharmaceutical Programmatic Collaboration for Management of Pretherapy and On-treatment Urinary Incontinence.

ABSTRACT: Many parenteral radiopharmaceuticals available as anticancer therapy are filtered by the kidneys and excreted in the urine. Here, physician leaders of radiation medicine, nuclear medicine/molecular imaging, and the radiotheranostics programs as well as radiation safety officers, collaborated to develop a decision-making guideline for the administration of therapeutic radiopharmaceuticals in patients with pretherapy or day-of-treatment incontinence. We discussed challenges and opportunities in the screening of patients in urine collection strategies according to grade of urinary incontinence and in subsequent coordination of care. Lutetium-177 ( 177 Lu)-based radiopharmaceutical therapies provided clinical examples of how our procedures were operationalized. Our key management issues of urinary incontinence were cutaneous radiation injury and redness, infection, or pain. In response, we developed clinical practice guidelines for the recognition and management of incontinence-related adverse events. Common adverse events of urinary incontinence were noted in this study. Our how-to guideline for the safe administration of therapeutic radiopharmaceuticals for patients with urinary incontinence warrants further investigation and should continue to be evaluated across all radiopharmaceutical therapy agents.

White matter hyperintensities influence distal cortical ß-amyloid accumulation in default mode network pathways.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid ß (Aß) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults. METHODS: Regional standard uptake value ratios (SUVr) from Aß-PET and white matter hyperintensity (WMH) volumes from three-dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini-mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aß-PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes. RESULTS: The regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p = .011). CONCLUSION: The findings suggest that the relation between Aß in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aß and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.

Molecular Tumor Board-Assisted Care in an Advanced Cancer Population: Results of a Phase II Clinical Trial.

PURPOSE: Multidisciplinary molecular tumor boards (MTBs) interpret next-generation sequencing reports and help oncologists determine best therapeutic options; however, there is a paucity of data regarding their clinical utility. The purpose of this study was to determine if MTB-directed therapy improves progression-free survival (PFS) over immediately prior therapy in patients with advanced cancer. METHODS: This single-arm, prospective phase II clinical trial enrolled patients with advanced cancer with an actionable mutation who received MTB-recommended targeted therapy between January 1, 2017, and October 31, 2020. MTB-recommended both on-label (level 1 evidence) and off-label (evidence levels 2 and 3) therapies. Of the 93 enrolled patients, 43 were treated frontline and 50 received second-line or greater-line therapy. The primary outcome was the probability of patients treated with second-line or greater-line MTB-directed therapy who achieved a PFS ratio ≥ 1.3 (PFS on MTB-directed therapy divided by PFS on the patient's immediately prior therapy). Secondary outcomes included PFS for patients treated frontline and overall survival and adverse effects for the entire study population. RESULTS: The most common disease sites were lung (35 of 93, 38%), gynecologic (17 of 93, 18%), GI (16 of 93, 17%), and head and neck (7 of 93, 8%). The Kaplan-Meier estimate of the probability of PFS ratio ≥ 1.3 was 0.59 (95% CI, 0.47 to 0.75) for patients treated with second-line or greater-line MTB-directed therapy. The median PFS was 449 (range 42-1,125) days for patients treated frontline. The median overall survival was 768 (range 22-1,240) days. There were four nontreatment-related deaths. CONCLUSION: When treated with MTB-directed therapy, most patients experienced improved PFS compared with immediately prior treatment. MTB-directed targeted therapy may be a strategy to improve outcomes for patients with advanced cancer.

Amyloid-PET Levels in the Precuneus and Posterior Cingulate Cortices Are Associated with Executive Function Scores in Preclinical Alzheimer's Disease Prior to Overt Global Amyloid Positivity.

BACKGROUND: Global amyloid-ß (Aß) deposition in the brain can be quantified by Aß-PET scans to support or refute a diagnosis of preclinical Alzheimer's disease (pAD). Yet, Aß-PET scans enable quantitative evaluation of regional Aß elevations in pAD, potentially allowing even earlier detection of pAD, long before global positivity is achieved. It remains unclear as to whether such regional changes are clinically meaningful. OBJECTIVE: Test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in pAD. METHODS: Global and regional standardized uptake value ratios (SUVr) from 18F-florbetapir PET/CT scanning were determined using the Siemens Syngo.via® Neurology software package across a sample of 99 clinically normal participants with Montreal Cognitive Assessment (MoCA) scores≥23. Relationships between regional SUVr and cognitive test scores were analyzed using linear regression models adjusted for age, sex, and education. Participants were divided into two groups based on SUVr in the posterior cingulate and precuneus gyri (SUVR≥1.17). Between group differences in cognitive test scores were analyzed using ANCOVA models. RESULTS: Executive function performance was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p < 0.05). There were no significant associations between memory and Aß-PET SUVr in any regions of the brain. CONCLUSION: These data demonstrate that increased Aß deposition in the precuneus and posterior cingulate (the earliest brain regions affected with Aß pathology) is associated with changes in executive function that may precede memory decline in pAD.

ACR Appropriateness Criteria® Noncerebral Vasculitis.

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Retroperitoneal Bleed.

The initial diagnosis of retroperitoneal bleeding can be challenging by physical examination and clinical presentation. Prompt imaging can make the diagnosis and be lifesaving. When selecting appropriate imaging for these patient's, consideration must be made for sensitivity and ability to image the retroperitoneum, as well as speed of imaging.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism.

BACKGROUNDBeige and brown adipose tissue (BAT) are associated with improved metabolic homeostasis. We recently reported that the ß3-adrenergic receptor agonist mirabegron induced beige adipose tissue in obese insulin-resistant subjects, and this was accompanied by improved glucose metabolism. Here we evaluated pioglitazone treatment with a combination pioglitazone and mirabegron treatment and compared these with previously published data evaluating mirabegron treatment alone. Both drugs were used at FDA-approved dosages.METHODSWe measured BAT by PET CT scans, measured beige adipose tissue by immunohistochemistry, and comprehensively characterized glucose and lipid homeostasis and insulin sensitivity by euglycemic clamp and oral glucose tolerance tests. Subcutaneous white adipose tissue, muscle fiber type composition and capillary density, lipotoxicity, and systemic inflammation were evaluated by immunohistochemistry, gene expression profiling, mass spectroscopy, and ELISAs.RESULTSTreatment with pioglitazone or the combination of pioglitazone and mirabegron increased beige adipose tissue protein marker expression and improved insulin sensitivity and glucose homeostasis, but neither treatment induced BAT in these obese subjects. When the magnitude of the responses to the treatments was evaluated, mirabegron was found to be the most effective at inducing beige adipose tissue. Although monotherapy with either mirabegron or pioglitazone induced adipose beiging, combination treatment resulted in less beiging than either alone. The 3 treatments also had different effects on muscle fiber type switching and capillary density.CONCLUSIONThe addition of pioglitazone to mirabegron treatment does not enhance beiging or increase BAT in obese insulin-resistant research participants.TRIAL REGISTRATIONClinicalTrials.gov NCT02919176.FUNDINGNIH DK112282 and P20GM103527 and Clinical and Translational Science Awards grant UL1TR001998.

Integrated Multiparametric Radiomics and Informatics System for Characterizing Breast Tumor Characteristics with the OncotypeDX Gene Assay.

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10-3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.

The ß3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans.

BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains ß3-adrenergic receptors (ß3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the ß3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after ß3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and ß cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in ß cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since ß cells and skeletal muscle do not express ß3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves ß cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol.

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid ß (Aß) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD. METHODS/DESIGN: Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aß levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aß levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aß SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use. DISCUSSION: This manuscript describes the protocol of INCREASE ("INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression"): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016.

Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals.

BACKGROUND: Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR10 benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. AIMS: In this study, we compared the predicted ARR10 obtained in each individual with plaque burden detected by coronary computed tomography angiography. METHODS AND RESULTS: Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (n = 70; 52% male; median age 56 years [interquartile range 51-64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR10 with statin in the entire cohort was 2.7% (1.5-4.6%) with a corresponding number needed to treat over 10 years of 36 (22-63). In subjects with an ARR10 benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (p = 0.02). CONCLUSION: These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk.

Optimization of free-breathing whole-heart 3-dimensional cardiac magnetic resonance imaging at 3 tesla to identify coronary vein anatomy and to compare with multidetector computed tomography.

OBJECTIVE: This study optimizes use of 3-T magnetic resonance imaging (MRI) to delineate coronary venous anatomy and compares 3-T MRI with multidetector computed tomography (MDCT) measurements. METHODS: The study population included 37 consecutive subjects (22 men, 19-71 years old). Whole-heart contrast-enhanced MRI images at 3 T were acquired using segmented k-space gradient echo with inversion recovery prepared technique. The MDCT images were obtained using nonionic iodinated contrast. RESULTS: The coronary sinus and great cardiac, posterior interventricular, and anterior interventricular veins were visualized in 100% of cases by both MRI and MDCT. Detection of the posterior vein of the left ventricle and the left marginal vein by MRI was 97% and 81%, respectively. Bland-Altman plots showed agreement in ostial diameter measured by both modalities with correlation coefficients ranging from 0.5 to 0.76. Vein length and distances also agreed closely. CONCLUSIONS: Free-breathing whole-heart 3-dimensional MRI at 3 T provides high-spatial-resolution images and could offer an alternative imaging technique instead of MDCT scans.

The effects of applying breast compression in dynamic contrast material-enhanced MR imaging.

PURPOSE: To evaluate the effects of breast compression on breast cancer masses, contrast material enhancement of glandular tissue, and quality of magnetic resonance (MR) images in the identification and characterization of breast lesions. MATERIALS AND METHODS: This was a HIPAA-compliant, institutional review board-approved retrospective study, with waiver of informed consent. Images from 300 MR imaging examinations in 149 women (mean age ± standard deviation, 51.5 years ± 10.9; age range, 22-76 years) were evaluated. The women underwent diagnostic MR imaging (no compression) and MR-guided biopsy (with compression) between June 2008 and February 2013. Breast compression was expressed as a percentage relative to the noncompressed breast. Percentage enhancement difference was calculated between noncompressed- and compressed-breast images obtained in early and delayed contrast-enhanced phases. Breast density, lesion type (mass vs non-masslike enhancement [NMLE]), lesion size, percentage compression, and kinetic curve type were evaluated. Linear regression, receiver operating characteristic (ROC) curve analysis, and κ test were performed. RESULTS: Mean percentage compression was 31.3% ± 9.2 (range, 5.8%-53.2%). Percentage enhancement was higher in noncompressed- versus compressed-breast studies in early (146% ± 66 vs 107% ± 42, respectively; P < .001) and delayed (158% ± 68 vs 107% ± 42, respectively; P = .1) phases. Among breast lesions, 12% (seven of 59) were significantly smaller when compressed, which led to underestimation of TNM classification (P < .001). Breast masses (n = 35) showed significantly higher early percentage enhancement (157% ± 71) than lesions with NMLE (n = 15, 120% ± 40; P = .02) and a percentage enhancement difference (47.5% ± 64 vs 17% ± 28, respectively; P = .023). Kinetic curve performance for identifying invasive cancer decreased after compression (area under ROC curve = 0.53 vs 0.71, respectively; P = .02). Breast compression resulted in complete loss of enhancement of nine of 210 lesions (4%). CONCLUSION: Breast compression during biopsy affected breast lesion detection, lesion size, and dynamic contrast-enhanced MR imaging interpretation and performance. Limiting the application of breast compression is recommended, except when clinically necessary.

Diffusion-weighted MRI for detecting and monitoring cancer: a review of current applications in body imaging.

Diffusion-weighted magnetic resonance imaging (MRI), which involves the acquisition of a magnetic resonance signal related to the Brownian motion of water protons in tissue, has become a useful technique for assessing tumors. In this article, we review the basic concepts, imaging strategies, and body applications of diffusion-weighted MRI in detecting and monitoring cancer.

3-T dynamic contrast-enhanced MRI of the breast: pharmacokinetic parameters versus conventional kinetic curve analysis.

OBJECTIVE: The purpose of this article is to evaluate the incremental value of pharmacokinetic analysis of dynamic contrast-enhanced (DCE) MRI compared with conventional breast MRI (morphology plus kinetic curve type analysis) in characterizing breast lesions as malignant or benign. SUBJECTS AND METHODS: Patients underwent 3D high-resolution T1-weighted contrast-enhanced MRI and DCE-MRI at 3 T and had pathology-proven diagnosis (95%) or more than 2 years of follow-up confirming lesion stability (5%). Lesions were identified using the high-spatial-resolution contrast-enhanced MRI. Morphologic features (margin, enhancement, and pattern) and conventional DCE-MRI results (kinetic curve types 1, 2, or 3) or pharmacokinetic parameters (forward volume transfer constant [K(trans)], reverse volume transfer constant [K(ep)], and the extravascular extracellular space volume per unit volume of tissue), were included in multivariate models for prediction of benign versus malignant diagnosis. RESULTS: Ninety-five patients with 101 lesions were included: 52% of patients were premenopausal and 48% were postmenopausal. Sixty-eight lesions (67.3%) were malignant and 33 (32.7%) were benign. There was a significant association between K(trans) and K(ep) and the diagnosis of benign versus malignant (p < 0.001). The area under the curve for morphologic features (lesion margin and enhancement pattern) was 0.85, whereas inclusion of K(trans) or K(ep) in the model showed similar modest improvement in performance (area under the curve, 0.88-0.89). For DCE-MRI, both pharmacokinetic modeling and kinetic curve type analysis improved characterization of malignant and benign breast lesions. A diagnostic model including lesion morphology plus either pharmacokinetic parameters or kinetic curve assessment showed similar diagnostic performance in characterizing breast lesions. CONCLUSION: The use of kinetic curve type assessment or pharmacokinetic modeling in conjunction with high-resolution 3D breast MRI appears to offer similar improvement in diagnostic performance. Although morphologic analysis alone provides good characterization of breast lesions on MRI as benign or malignant, analysis of the lesion perfusion on DCE-MRI using either kinetic curve shape assessment or a pharmacokinetic modeling approach improves diagnostic accuracy.

Principles and applications of diffusion-weighted imaging in cancer detection, staging, and treatment follow-up.

Diffusion-weighted imaging relies on the detection of the random microscopic motion of free water molecules known as Brownian movement. With the development of new magnetic resonance (MR) imaging technologies and stronger diffusion gradients, recent applications of diffusion-weighted imaging in whole-body imaging have attracted considerable attention, especially in the field of oncology. Diffusion-weighted imaging is being established as a pivotal aspect of MR imaging in the evaluation of specific organs, including the breast, liver, kidney, and those in the pelvis. When used in conjunction with apparent diffusion coefficient mapping, diffusion-weighted imaging provides information about the functional environment of water in tissues, thereby augmenting the morphologic information provided by conventional MR imaging. Detected changes include shifts of water from extracellular to intracellular spaces, restriction of cellular membrane permeability, increased cellular density, and disruption of cellular membrane depolarization. These findings are commonly associated with malignancies; therefore, diffusion-weighted imaging has many applications in oncologic imaging and can aid in tumor detection and characterization and in the prediction and assessment of response to therapy.

An anthropomorphic phantom for quantitative evaluation of breast MRI.

PURPOSE: In this study, the authors aim to develop a physical, tissue-mimicking phantom for quantitative evaluation of breast MRI protocols. The objective of this phantom is to address the need for improved standardization in breast MRI and provide a platform for evaluating the influence of image protocol parameters on lesion detection and discrimination. Quantitative comparisons between patient and phantom image properties are presented. METHODS: The phantom is constructed using a mixture of lard and egg whites, resulting in a random structure with separate adipose- and glandular-mimicking components. T1 and T2 relaxation times of the lard and egg components of the phantom were estimated at 1.5 T from inversion recovery and spin-echo scans, respectively, using maximum-likelihood methods. The image structure was examined quantitatively by calculating and comparing spatial covariance matrices of phantom and patient images. A static, enhancing lesion was introduced by creating a hollow mold with stereolithography and filling it with a gadolinium-doped water solution. RESULTS: Measured phantom relaxation values fall within 2 standard errors of human values from the literature and are reasonably stable over 9 months of testing. Comparison of the covariance matrices of phantom and patient data demonstrates that the phantom and patient data have similar image structure. Their covariance matrices are the same to within error bars in the anterior-posterior direction and to within about two error bars in the right-left direction. The signal from the phantom's adipose-mimicking material can be suppressed using active fat-suppression protocols. A static, enhancing lesion can also be included with the ability to change morphology and contrast agent concentration. CONCLUSIONS: The authors have constructed a phantom and demonstrated its ability to mimic human breast images in terms of key physical properties that are relevant to breast MRI. This phantom provides a platform for the optimization and standardization of breast MRI imaging protocols for lesion detection and characterization.

Relationship of temporal resolution to diagnostic performance for dynamic contrast enhanced MRI of the breast.

PURPOSE: To investigate the relationship between temporal resolution of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and classification of breast lesions as benign versus malignant. MATERIALS AND METHODS: Patients underwent T(1)-weighted DCE MRI with 15 s/acquisition temporal resolution using 1.5 Tesla (n = 48) and 3.0T (n = 33) MRI scanners. Seventy-nine patients had pathologically proven diagnosis and 2 had 2 years follow-up showing no change in lesion size. The temporal resolution of DCE MRI was systematically reduced as a postprocessing step from 15 to 30, 45, and 60 s/acquisition by eliminating intermediate time points. Average wash-in and wash-out slopes, wash-out percentage changes, and kinetic curve shape (persistently enhancing, plateau, or wash-out) were compared for each temporal resolution. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to compare kinetic parameters and diagnostic accuracy. RESULTS: Sixty patients (74%) had malignant lesions and 21 patients (26%) had benign lesions. All temporal-resolution parameters significantly predicted benign versus malignant diagnosis (P < 0.05). However, 45 s/acquisition and higher temporal-resolution datasets showed higher accuracy than the 60 s/acquisition dataset by ROC curve analysis (0.72 versus 0.69 for average wash-in slope; 0.85 versus 0.82, for average wash-out slope; and 0.88 versus 0.80 for kinetic curve shape assessment, for 45 s/acquisition versus 60 s/acquisition temporal-resolution datasets, respectively (P = 0.027). CONCLUSION: DCE MRI data with at least 45-s temporal resolution maximized the agreement between the kinetic parameters and correct classification of benign versus malignant diagnosis.

Dynamic contrast-enhanced MRI of the breast: quantitative method for kinetic curve type assessment.

OBJECTIVE: The type of contrast enhancement kinetic curve (i.e., persistently enhancing, plateau, or washout) seen on dynamic contrast-enhanced MRI (DCE-MRI) of the breast is predictive of malignancy. Qualitative estimates of the type of curve are most commonly used for interpretation of DCE-MRI. The purpose of this study was to compare qualitative and quantitative methods for determining the type of contrast enhancement kinetic curve on DCE-MRI. MATERIALS AND METHODS: Ninety-six patients underwent breast DCE-MRI. The type of DCE-MRI kinetic curve was assessed qualitatively by three radiologists on two occasions. For quantitative assessment, the slope of the washout curve was calculated. Kappa statistics were used to determine inter- and intraobserver agreement for the qualitative method. Matched sample tables, the McNemar test, and receiver operating characteristic (ROC) curve statistics were used to compare quantitative versus qualitative methods for establishing or excluding malignancy. RESULTS: Seventy-eight lesions (77.2%) were malignant and 23 (22.8%) were benign. For the qualitative assessment, the intra- and interobserver agreement was good (kappa = 0.76-0.88), with an area under the ROC curve (AUC) of 0.73-0.77. For the quantitative method, the highest AUC was 0.87, reflecting significantly higher diagnostic accuracies compared with qualitative assessment (p < 0.01 for the difference between the two methods). CONCLUSION: Quantitative assessment of the type of contrast enhancement kinetic curve on breast DCE-MRI resulted in significantly higher diagnostic performance for establishing or excluding malignancy compared with assessment based on the standard qualitative method.