Breast lesions classified as probably benign (BI-RADS 3) on magnetic resonance imaging: a systematic review and meta-analysis.

PURPOSE: To investigate prevalence, malignancy rates, imaging features, and follow-up intervals for probably benign (BI-RADS 3) lesions on breast magnetic resonance imaging (MRI). METHODS: A systematic database-review of articles published through 22/06/2016 was performed. Eligible studies reported BI-RADS 3 lesions on breast MRI. Two independent reviewers performed a literature review and data extraction. Data collection included study characteristics, number/type of BI-RADS 3 lesions, final diagnosis (histopathology and/or follow-up). Sources of bias (QUADAS-2) were assessed. Meta-analysis included data-pooling, heterogeneity testing, and meta-regression. RESULTS: Fifteen studies were included. Prevalence was reported in 11 studies (range: 1.2-24.3%). Malignancy rates ranged between 0.5-10.1% (pooled 61/2814, 1.6%, 95%-CI:0.9-2.3% (random-effects-model), I2=53%, P=0.007). In a subgroup of 11 studies (2183 lesions), highest malignancy rates were observed in non-mass lesions (pooled 25/714, 2.3%, 95%-CI:0.8-3.9%, I2=52%, P=0.021) followed by mass lesions (pooled 15/771, 1.5%, 95%-CI:0.7-2.4%, I2=0%, P=0.929), and foci (pooled 10/698, 1%, 95%-CI:0.3-1.7%, I2=0%, P=0.800). There was non-significant negative association between prevalence and malignancy rates (P=0.077). Malignant lesions were diagnosed at all follow-up time points. CONCLUSION: While prevalence of MRI BI-RADS 3 lesions was strongly heterogeneous, pooled malignancy rates met BI-RADS benchmarks (<2%). Malignancy rates varied, exceeding 2% in non-mass lesions. Twenty-four-month surveillance is required to detect all malignant lesions. KEY POINTS: • Probably benign (BI-RADS 3) lesions showed a pooled malignancy-rate of 1.6% (95%-CI:0.9-2.3%). • Malignancy rates differ and are highest in non-mass lesions (2.3%, 95%-CI:0.8-3.9%). • The prevalence of BI-RADS 3 lesions on breast MRI ranged from 1.2-24.3%. • Malignant lesions were diagnosed at follow-up time points up to 24 months.

3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.

OBJECTIVES: To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. METHODS: This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). CONCLUSIONS: Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. KEY POINTS: • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.

Diffusion-weighted imaging of breast lesions: Region-of-interest placement and different ADC parameters influence apparent diffusion coefficient values.

OBJECTIVES: To investigate the influence of region-of-interest (ROI) placement and different apparent diffusion coefficient (ADC) parameters on ADC values, diagnostic performance, reproducibility and measurement time in breast tumours. METHODS: In this IRB-approved, retrospective study, 149 histopathologically proven breast tumours (109 malignant, 40 benign) in 147 women (mean age 53.2) were investigated. Three radiologists independently measured minimum, mean and maximum ADC, each using three ROI placement approaches:1 - small 2D-ROI, 2 - large 2D-ROI and 3 - 3D-ROI covering the whole lesion. One reader performed all measurements twice. Median ADC values, diagnostic performance, reproducibility, and measurement time were calculated and compared between all combinations of ROI placement approaches and ADC parameters. RESULTS: Median ADC values differed significantly between the ROI placement approaches (p < .001). Minimum ADC showed the best diagnostic performance (AUC .928-.956), followed by mean ADC obtained from 2D ROIs (.926-.94). Minimum and mean ADC showed high intra- (ICC .85-.94) and inter-reader reproducibility (ICC .74-.94). Median measurement time was significantly shorter for the 2D ROIs (p < .001). CONCLUSIONS: ROI placement significantly influences ADC values measured in breast tumours. Minimum and mean ADC acquired from 2D-ROIs are useful for the differentiation of benign and malignant breast lesions, and are highly reproducible, with rapid measurement. KEY POINTS: • Region of interest placement significantly influences apparent diffusion coefficient of breast tumours. • Minimum and mean apparent diffusion coefficient perform best and are reproducible. • 2D regions of interest perform best and provide rapid measurement times.

A simple classification system (the Tree flowchart) for breast MRI can reduce the number of unnecessary biopsies in MRI-only lesions.

OBJECTIVES: To assess whether using the Tree flowchart obviates unnecessary magnetic resonance imaging (MRI)-guided biopsies in breast lesions only visible on MRI. METHODS: This retrospective IRB-approved study evaluated consecutive suspicious (BI-RADS 4) breast lesions only visible on MRI that were referred to our institution for MRI-guided biopsy. All lesions were evaluated according to the Tree flowchart for breast MRI by experienced readers. The Tree flowchart is a decision rule that assigns levels of suspicion to specific combinations of diagnostic criteria. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy. To assess reproducibility by kappa statistics, a second reader rated a subset of 82 patients. RESULTS: There were 454 patients with 469 histopathologically verified lesions included (98 malignant, 371 benign lesions). The area under the curve (AUC) of the Tree flowchart was 0.873 (95% CI: 0.839-0.901). The inter-reader agreement was almost perfect (kappa: 0.944; 95% CI 0.889-0.998). ROC analysis revealed exclusively benign lesions if the Tree node was ≤2, potentially avoiding unnecessary biopsies in 103 cases (27.8%). CONCLUSIONS: Using the Tree flowchart in breast lesions only visible on MRI, more than 25% of biopsies could be avoided without missing any breast cancer. KEY POINTS: • The Tree flowchart may obviate >25% of unnecessary MRI-guided breast biopsies. • This decrease in MRI-guided biopsies does not cause any false-negative cases. • The Tree flowchart predicts 30.6% of malignancies with >98% specificity. • The Tree's high specificity aids in decision-making after benign biopsy results.

Malignancy rates and diagnostic performance of the Bosniak classification for the diagnosis of cystic renal lesions in computed tomography - a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the Bosniak classification system in CT to determine its diagnostic performance to diagnose malignant cystic lesions and the prevalence of malignancy in Bosniak categories. METHODS: A predefined database search was performed from 1 January 1986 to 18 January 2016. Two independent reviewers extracted data on malignancy rates in Bosniak categories and several covariates using predefined criteria. Study quality was assessed using QUADAS-2. Meta-analysis included data pooling, subgroup analyses, meta-regression and investigation of publication bias. RESULTS: A total of 35 studies, which included 2,578 lesions, were investigated. Data on observer experience, inter-observer variation and technical CT standards were insufficiently reported. The pooled rate of malignancy increased from Bosniak I (3.2 %, 95 % CI 0-6.8, I2 = 5 %) to Bosniak II (6 %, 95 % CI 2.7-9.3, I2 = 32 %), IIF (6.7 %, 95 % CI 5-8.4, I2 = 0 %), III (55.1 %, 95 % CI 45.7-64.5, I2 = 89 %) and IV (91 %, 95 % CI 87.7-94.2, I2 = 36). Several study design-related influences on malignancy rates and subsequent diagnostic performance indices were identified. CONCLUSION: The Bosniak classification is an accurate tool with which to stratify the risk of malignancy in renal cystic lesions. KEY POINTS: • The Bosniak classification can accurately rule out malignancy. • Specificity remains moderate at 74 % (95 % CI 64-82). • Follow-up examinations should be considered in Bosniak IIF and Bosniak II cysts. • Data on the influence of reader experience and inter-reader variability are insufficient. • Technical CT standards and publication year did not influence diagnostic performance.

Clinical application of Acoustic Radiation Force Impulse Imaging with Virtual Touch IQ in breast ultrasound: diagnostic performance and reproducibility of a new technique.

Background Virtual Touch IQ (VTIQ) is a novel technique of quantitative sonoelastography that applies acoustic radiation force impulse (ARFI). Purpose To evaluate breast ARFI imaging with VTIQ in the clinical setting, with regard to reproducibility and diagnostic performance, and to specify cutoff limits for the differentiation of benign and malignant lesions. Material and Methods This retrospective study included 83 patients with 85 breast lesions (51 benign, 34 malignant) who received ARFI imaging with VTIQ. Two independent ARFI measurements of each lesion were performed and shear wave velocities (SWV) of the lesion and the adjacent tissues were measured. A lesion-to-fat velocity ratio (L/F Ratio) was calculated for each lesion. Diagnostic performance of SWV measurements and L/F Ratios was evaluated with receiver operating curve (ROC) analysis. The intraclass correlation coefficient and Bland-Altman plots were used to evaluate measurement reproducibility. Results All measurements showed equal diagnostic performance, as measured by the area under the ROC curve (0.853 for SWV, 0.882 for the L/F Ratio). At a cutoff value of 3.23 m/s, sensitivity and specificity were 82.4% and 80.4%, respectively. An L/F Ratio cutoff value of 2.23 revealed a sensitivity and specificity of 89.7% and 76.5%. The reproducibility of the SWV measurements was moderate (limits of agreement, 40.3-44.4%) and higher than that of the L/F Ratios (54.5-60.2%). Conclusion ARFI imaging with VTIQ is a novel, moderately reproducible, quantitative elastography technique, which provides useful information for the differentiation of benign and malignant breast lesions in the clinical setting.

Diffusion-weighted MRI of breast lesions: a prospective clinical investigation of the quantitative imaging biomarker characteristics of reproducibility, repeatability, and diagnostic accuracy.

Diffusion-weighted MRI (DWI) provides insights into tissue microstructure by visualization and quantification of water diffusivity. Quantitative evaluation of the apparent diffusion coefficient (ADC) obtained from DWI has been proven helpful for differentiating between malignant and benign breast lesions, for cancer subtyping in breast cancer patients, and for prediction of response to neoadjuvant chemotherapy. However, to further establish DWI of breast lesions it is important to evaluate the quantitative imaging biomarker (QIB) characteristics of reproducibility, repeatability, and diagnostic accuracy. In this intra-individual prospective clinical study 40 consecutive patients with suspicious findings, scheduled for biopsy, underwent an identical 3T breast MRI protocol of the breast on two consecutive days (>24 h). Mean ADC of target lesions was assessed (two independent readers) in four separate sessions. Reproducibility, repeatability, and diagnostic accuracy between examinations (E1, E2), readers (R1, R2), and measurements (M1, M2) were assessed with intraclass correlation coefficients (ICCs), coefficients of variation (CVs), Bland-Altman plots, and receiver operating characteristic (ROC) analysis with calculation of the area under the ROC curve (AUC). The standard of reference was either histopathology (n = 38) or imaging follow-up of up to 24 months (n = 2). Eighty breast MRI examinations (median E1-E2, 2 ± 1.7 days, 95% confidence interval (CI) 1-2 days, range 1-11 days) in 40 patients (mean age 56, standard deviation (SD) ±14) were evaluated. In 55 target lesions (mean size 25.2 ± 20.8 (SD) mm, range 6-106 mm), mean ADC values were significantly (P < 0.0001) higher in benign (1.38, 95% CI 1.27-1.49 × 10(-3)  mm(2) /s) compared with malignant (0.86, 95% CI 0.81-0.91 × 10(-) (3)  mm(2) /s) lesions. Reproducibility and repeatability showed high agreement for repeated examinations, readers, and measurements (all ICCs >0.9, CVs 3.2-8%), indicating little variation. Bland-Altman plots demonstrated no systematic differences, and diagnostic accuracy was not significantly different in the two repeated examinations (all ROC curves >0.91, P > 0.05). High reproducibility, repeatability, and diagnostic accuracy of DWI provide reliable characteristics for its use as a potential QIB, to further improve breast lesion detection, characterization, and treatment monitoring of breast lesions.

Synthesis and preclinical evaluation of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand.

PURPOSE: The aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined. METHODS: Several conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed. RESULTS: Quantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv. CONCLUSION: 18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.

Multiparametric MRI of the prostate at 3 T: limited value of 3D (1)H-MR spectroscopy as a fourth parameter.

PURPOSE: The aim of our study was to assess whether multiparametric magnetic resonance imaging (MP-MRI) of the prostate with three parameters (PS3: T2-weighted, DWI, and DCE) benefits from an additional fourth parameter (PS4: including (1)H-MRSI) in the detection and grading of prostate cancer (PCa) at 3 T. METHODS: MP-MRI was performed in 64 patients (mean 66.7 years, mean PSA 13 ng/ml). Reference standard was obtained by histopathology. Two readers independently evaluated the images. A summation score of each individual parameter for three parameters (PS3) and for four parameters (PS4) was calculated. RESULTS: In 52 (81.3 %) of 64 patients, histopathology confirmed a PCa. The diagnostic performance for PCa detection of PS4 (O1: 91.7 %, O2: 91.3 %) equaled that of PS3 (O1: 92.8 %, O2: 92.2 %, P > 0.05). Prediction of high-grade PCa by PS4 (O1: 75.1 %, O2: 74.7 %) was as good as with PS3 (O1: 75.1 %, O2: 72.8 %, P > 0.05). Kappa agreement between the two readers was substantial (0.734 PS4) to moderate (0.558 PS3). CONCLUSIONS: MP-MRI with four parameters including (1)H-MRSI does not increase the detection and grading of prostate cancer at 3 T compared to MP-MRI with three parameters. A sum score accurately detects PCa at 3 T without an endorectal coil and shows potential for the prediction of tumor grade.

MR-guided vacuum-assisted breast biopsy of MRI-only lesions: a single center experience.

PURPOSE: The purpose of this study was to compare three different biopsy devices on false-negative and underestimation rates in MR-guided, vacuum-assisted breast biopsy (VABB) of MRI-only lesions. METHODS: This retrospective, single-center study was IRB-approved. Informed consent was waived. 467 consecutive patients underwent 487 MR-guided VABB using three different 8-10-gauge-VABB devices (Atec-9-gauge,A; Mammotome-8-gauge,M; Vacora-10-gauge,V). VABB data (lesion-type, size, biopsy device, histopathology) were compared to final diagnosis (surgery, n = 210 and follow-up, n = 277). Chi-square, and Kruskal-Wallis tests were applied. P values < 0.05 were considered significant. RESULTS: Final diagnosis was malignant in 104 (21.4 %), high risk in 64 (13.1 %) and benign in 319 (65.5 %) cases. Eleven of 328 (3.4 %) benign-rated lesions were false-negative (1/95, 1.1 %, A; 2/73, 2.7 %, M; 8/160 5.0 % V; P = 0.095). Eleven high-risk (11/77, 14.3 %) lesions proved to be malignant (3/26, 11.5 % A; 4/12, 33.3 % M; 4/39, 10.3 % V; P = 0.228). Five of 34 (14.7 %) DCIS were upgraded to invasive cancer (2/15, 13.3 %, A; 1/6, 16.6 % M; 2/13, 15.3 %, V; P = 0.977). Lesion size (P = 0.05) and type (mass vs. non-mass, P = 0.107) did not differ significantly. CONCLUSION: MR-guided VABB is an accurate method for diagnosis of MRI-only lesions. No significant differences on false-negative and underestimation rates were observed between three different biopsy devices. KEY POINTS: • MR-guided VABB is an accurate procedure for the diagnosis of MRI-only lesions. • Similar false-negative and underestimation rates allow all three different MR-guided VABB devices for clinical application. • High-risk lesions should undergo surgery due to a substantial underestimation rate. • Agreement between MR-guided VABB and final diagnosis (benign/malignant) was 95.5% (465/487).

Diagnostic utility of second-look US for breast lesions identified at MR imaging: systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic utility of second-look ultrasonography (US) in the assessment of lesions identified at breast magnetic resonance (MR) imaging. MATERIALS AND METHODS: A systematic review of the PubMed database for articles published up to January 6, 2013, was performed by using predefined search terms applied in a standardized manner. Second-look US studies for the assessment of breast lesions identified at MR imaging were eligible for this meta-analysis. Two independent reviewers performed the literature review and data extraction. Eligible studies presented data on the number of lesions examined and the number of lesions detected at second-look US. The reference standard for lesion diagnosis was either histopathologic or follow-up examination. Sources of bias were assessed by using the Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2 Quality Assessment of Diagnostic Accuracy Studies 2 , tool. Statistical analysis included data pooling, heterogeneity testing, and meta-regression. RESULTS: Seventeen studies that included benign and malignant lesions met the inclusion criteria. The general lesion detection rate at second-look US was very heterogeneous and ranged between 22.6% and 82.1% (pooled rate, 57.5% [1266 of 2201]; 95% confidence interval [ CI confidence interval ]: 50.0%, 64.1% [random-effects model]; I(2) = 90.9%; P < .0001). The highest second-look US detection rates were observed for mass lesions (as opposed to nonmass lesions) and malignant (vs benign) lesions (P < .001 for both). Pooled positive and negative predictive values (positive or negative second-look US correlates of MR imaging-detected malignant or benign lesions) were calculated as 30.7% (95% CI confidence interval : 25.3%, 36.4%; I(2) = 75.4%; P < .0001) and 87.8% (95% CI confidence interval : 82.0%, 92.7%; I(2) = 82.1%; P < .0001), respectively, by using random-effects models. CONCLUSION: The results of this study demonstrated variable utility of second-look US in MR imaging-detected lesions, as lesion detection rates were very heterogeneous. Subgroup analysis showed that malignant and mass lesions were more likely to be detected at second-look US. Furthermore, malignancy was not excluded if a lesion was not detected at second-look US.

MRI-only lesions: application of diffusion-weighted imaging obviates unnecessary MR-guided breast biopsies.

OBJECTIVE: To assess if the application of diffusion-weighted imaging (DWI) obviates unnecessary MR-guided biopsies in suspicious breast lesions visible only on contrast-enhanced MRI (CE-MRI). METHODS: This institutional review board (IRB)-approved, retrospective, single-centre study included 101 patients (mean age, 49.5; SD 13.9 years) who underwent additional DWI at 1.5 T prior to MRI-guided biopsy of 104 lesions classified as suspicious for malignancy and visible on CE-MRI only. An experienced radiologist, blinded to histopathologic and follow-up results, measured apparent diffusion coefficient (ADC) values obtained from DWI. Diagnostic accuracy was investigated using receiver operating characteristics (ROC) analysis. RESULTS: Histopathology revealed 20 malignant and 84 benign lesions. Lesions were masses in 61 (15 malignant, 24.6 %) and non-masses in 43 cases (five malignant, 11.6 %). Mean ADC values were 1.53 ± 0.38 × 10(-3) mm(2)/s in benign lesions and 1.06 ± 0.27 × 10(-3) mm(2)/s in malignant lesions. ROC analysis revealed exclusively benign lesions if ADC values were greater than 1.58 × 10(-3) mm(2)/s. As a consequence, 29 false-positive biopsies (34.5 %) could have been avoided without any false-negative findings. Both in mass and in non-mass lesions, rule-in and rule-out criteria were identified using flexible ADC thresholds based on ROC analysis. CONCLUSION: Additional application of DWI in breast lesions visible only on MRI can avoid false-positive, MR-guided biopsies. Thus, DWI should be an integral part of breast MRI protocols. KEY POINTS: DWI measurements are a fast and helpful technique for improved breast lesion diagnosis. DWI application in breast lesions visible only on MRI obviates false-positive, MR-guided biopsies. Flexible ADC thresholds provide rule-in and rule-out criteria for breast lesion malignancy.

Rate of malignancy in MRI-detected probably benign (BI-RADS 3) lesions.

OBJECTIVE: The purpose of this study was to evaluate the malignancy rate in MRI-detected probably benign (BI-RADS 3) lesions in women without a history of breast cancer. MATERIALS AND METHODS: In this study, 1265 patients underwent breast MRI during a 7-year period. One hundred and eight (8.5%) patients with a nonpalpable breast lesion classified as BI-RADS 3 at MRI and with a needle biopsy or adequate follow-up of at least 24 months were included. Statistical analysis included calculation of the negative predictive value with its 95% CI. RESULTS: Of 108 lesions, 107 (99.1%) were correctly assessed as probably benign, resulting in a negative predictive value of 99.1% (95% CI, 94.99-99.98%). Histopathology was requested by the patient or referring physician in 44 patients. Of these, 43 (39.8%) lesions were classified as benign and one (0.9%) as malignant. There were no changes evident in any of the remaining 64 (59.2%) lesions during follow-up (range, 2-9 years). CONCLUSION: In MRI-detected probably benign (BI-RADS 3) lesions, the malignancy rate is low and within the accepted cancer rate for mammographically or sonographically detected BI-RADS 3 lesions. Short-term follow-up MRI at intervals of 6, 12, and 24 months in MRI BI-RADS 3 lesions remains a strong tool with which to detect suspicious lesions. Interval changes in size, morphology, or enhancement are regarded as indicative of malignancy.

3'-deoxy-3'-[18F]fluorothymidine positron emission tomography for response assessment in soft tissue sarcoma: a pilot study to correlate imaging findings with tissue thymidine kinase 1 and Ki-67 activity and histopathologic response.

BACKGROUND: This study sought to determine whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging allows assessment of tumor viability and proliferation in patients with soft tissue sarcomas who are treated with neoadjuvant therapy. METHODS: Twenty patients with biopsy-proven, resectable, high-grade soft tissue sarcoma underwent [(18)F]FLT PET/CT imaging before and after neoadjuvant therapy. Histologic subtypes included sarcomas not otherwise specified (n = 5), malignant peripheral nerve sheath tumors (n = 3), gastrointestinal stromal tumors (n = 3), leiomyosarcomas (n = 3), angiosarcomas (n = 2), and others (n = 4). Changes in [(18)F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [(18)F]FLT tumor uptake was correlated with thymidine kinase 1 (TK1) expression and Ki-67 staining indices in excised tumor tissue. RESULTS: Tumor FLT SUVpeak averaged 7.1 ± 3.7 g/mL (range, 1.9-16.1 g/mL) at baseline and decreased significantly to 2.7 ± 1.6 g/mL (range, 0.8-6.0 g/mL) at follow-up (P < .001); however, marked reductions in SUV were not specific for histopathological response. The posttreatment SUVpeak did not correlate with TK1 (P = .27) or Ki-67 expression (P = .21). CONCLUSIONS: Marked reductions in [(18)F]FLT tumor uptake in response to neoadjuvant treatment were observed in most patients with sarcoma. However, these reductions were not specific for histopathologic response to neoadjuvant therapy. Furthermore, posttreatment [(18)F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [(18)F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.

Quantitative Apparent Diffusion Coefficient Derived From Diffusion-Weighted Imaging Has the Potential to Avoid Unnecessary MRI-Guided Biopsies of mpMRI-Detected PI-RADS 4 and 5 Lesions.

OBJECTIVE: The aim of this study was to evaluate the potential of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) measurements to obviate unnecessary biopsies in multiparametric MRI-detected PI-RADS 4 and 5 lesions. MATERIALS AND METHODS: This retrospective, institutional review board-approved study investigated 101 PI-RADS 4 and 5 prostate lesions (52 malignant, 49 benign) verified by in-bore MRI-guided biopsy in 101 men (mean age, 62.8 years). Two readers, who were not aware of the biopsy results independently and repeatedly measured minimum, mean, and maximum ADC from diffusion-weighted imaging measurements (in line with PI-RADS v2 recommendations) using a 2-dimensional region of interest drawn around the biopsied lesions. Diagnostic performance was evaluated using receiver operating characteristic statistics and reproducibility statistics were calculated. RESULTS: The best diagnostic performance (overall area under the receiver operating characteristic curve [AUC] R1: 0.801; R2: 0.796 peripheral zone AUC R1:0.814, R2: 0.805; transitional zone AUC R1:0.786, R2:0.779) and the tightest limits of interreader agreement (-8.6% to 9.9%) were found in minimum ADC values. Rule-in and rule-out thresholds for diagnosis of prostate cancer were identified, demonstrating a potential to avoid unnecessary biopsies in 32.7% (16/49). CONCLUSIONS: Quantitative ADC measurement in multiparametric MRI-detected PI-RADS 4 and 5 lesions has the potential to avoid unnecessary MRI-guided biopsies in up to 33%.

Potential of Noncontrast Magnetic Resonance Imaging With Diffusion-Weighted Imaging in Characterization of Breast Lesions: Intraindividual Comparison With Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVES: The aim of this study was to assess the potential of noncontrast magnetic resonance imaging (NC-MRI) with diffusion-weighted imaging (DWI) in characterization of breast lesions in comparison to dynamic contrast-enhanced MRI (DCE-MRI) at 3 T. MATERIALS AND METHODS: Consecutive patients with conventional imaging (mammography, ultrasound) BI-RADS 4/5 findings were included in this institutional review board-approved single-center study. All underwent 3 T breast MRI including readout-segmented DWI, DCE, and T2-weighted sequences. Final diagnosis was defined by histopathology or follow-up (>24 months). Two experienced radiologists (R1, R2) independently assigned lesion conspicuity (0 = minimal to 3 = excellent) and BI-RADS scores to NC-MRI (readout-segmented DWI including apparent diffusion coefficient maps) and DCE-MRI (DCE and T2-weighted). Receiver operating characteristics, κ statistics, and visual grading characteristics analysis were applied. RESULTS: Sixty-seven malignant and 56 benign lesions were identified in 113 patients (mean age, 54 ± 14 years). Areas under the receiver operating characteristics curves were similar: DCE-MRI: 0.901 (R1), 0.905 (R2); NC-MRI: 0.882 (R1), 0.854 (R2); P > 0.05, respectively. The κ agreement was 0.968 (DCE-MRI) and 0.893 (NC-MRI). Visual grading characteristics analysis revealed superior lesion conspicuity by DCE-MRI (0.661, P < 0.001). CONCLUSIONS: Diagnostic performance and interreader agreement of both NC-MRI and DCE-MRI is high, indicating a potential use of NC-MRI as an alternative to DCE-MRI. However, inferior lesion conspicuity and lower interreader agreement of NC-MRI need to be considered.

3 Tesla breast MR imaging as a problem-solving tool: Diagnostic performance and incidental lesions.

PURPOSE: To investigate the diagnostic performance and incidental lesion yield of 3T breast MRI if used as a problem-solving tool. METHODS: This retrospective, IRB-approved, cross-sectional, single-center study comprised 302 consecutive women (mean: 50±12 years; range: 20-79 years) who were undergoing 3T breast MRI between 03/2013-12/2014 for further workup of conventional and clinical breast findings. Images were read by experienced, board-certified radiologists. The reference standard was histopathology or follow-up ≥ two years. Sensitivity, specificity, PPV, and NPV were calculated. Results were stratified by conventional and clinical breast findings. RESULTS: The reference standard revealed 53 true-positive, 243 true-negative, 20 false-positive, and two false-negative breast MRI findings, resulting in a sensitivity, specificity, PPV, and NPV of 96.4% (53/55), 92.4% (243/263), 72.6% (53/73), and 99.2% (243/245), respectively. In 5.3% (16/302) of all patients, incidental MRI lesions classified BI-RADS 3-5 were detected, 37.5% (6/16) of which were malignant. Breast composition and the imaging findings that had led to referral had no significant influence on the diagnostic performance of breast MR imaging (p>0.05). CONCLUSION: 3T breast MRI yields excellent diagnostic results if used as a problem-solving tool independent of referral reasons. The number of suspicious incidental lesions detected by MRI is low, but is associated with a substantial malignancy rate.

Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway.

18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors.

68Ga-DOTATATE PET/CT Interobserver Agreement for Neuroendocrine Tumor Assessment: Results of a Prospective Study on 50 Patients.

We evaluated observer agreement for 68Ga-DOTATATE PET/CT interpretations in patients with neuroendocrine tumor (NET). METHODS: 68Ga-DOTATATE PET/CT was performed on 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4), or other location (n = 13). The images were reviewed by 7 observers, who used a standardized interpretation approach. The observers were classified as having a low level of experience (<500 scans or <5 y experience with 68Ga-DOTATATE PET/CT; n = 4) or a high level of experience (≥500 scans or ≥5 y experience with 68Ga-DOTATATE PET/CT; n = 3). Interpretation by the primary nuclear medicine physician, who had access to all clinical and imaging data, served as the reference standard. Interobserver agreement was determined by the Cohen κ statistic and intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95%CI). RESULTS: Interobserver agreement was substantial, and the median number of false findings was low for the overall scan result: that is, positive versus negative scan result (κ = 0.80; 95%CI, 0.74-0.86; false findings, 3), organ involvement (κ = 0.70; 95%CI, 0.64-0.76; false findings, 5), and lymph node involvement (κ = 0.71; 95%CI, 0.65-0.78; false findings, 6). Interobserver agreement was substantial to almost perfect, and the average absolute difference (Δ) from the reference observer was low for number of organ and lymph node metastases (organ: ICC, 0.84; 95%CI, 0.77-0.89; Δ = 0.45; lymph node: ICC, 0.77; 95%CI, 0.69-0.84; Δ = 0.45), tumor SUVmax (ICC, 0.99; 95%CI, 0.97-0.99; Δ = 0.44), and reference SUV (spleen: ICC, 0.81; Δ = 1.10; liver: ICC, 0.79; Δ = 0.62). Interpretations of appropriateness for peptide-receptor radionuclide therapy varied more significantly among observers (κ = 0.64; 95%CI, 0.57-0.70), and a higher frequency of false-positive recommendations for peptide-receptor radionuclide therapy occurred in observers with low experience than in those with high experience (range, 7-12 vs. 4-8). CONCLUSION: The interpretation of 68Ga-DOTATATE PET/CT images for NET staging is consistent among observers with low and high levels of experience. However, image-based recommendations for or against peptide-receptor radionuclide therapy require experience and training.