Genitourinary Imaging Original Research

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1 Genitourinary Imaging Original Research Murray et al. Detection of Intratumoral Hemorrhage Within Papillary RCC on T1-Weighted MRI Genitourinary Imaging Original Research Catherine A. Murray 1 Matthew Quon 1 Matthew D. F. McInnes 1 Christian B. van der Pol 1 Shaheed W. Hakim 2 Trevor A. Flood 2 Nicola Schieda 1 Murray CA, Quon M, McInnes MDF, et al. Keywords: angiomyolipoma, hemorrhage, MRI, papillary, renal cell carcinoma DOI: /AJR Received January 5, 2016; accepted after revision March 29, Department of Medical Imaging, The Ottawa Hospital, The University of Ottawa, 1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. Address correspondence to N. Schieda (nschieda@toh.on.ca). 2 Department of Anatomical Pathology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON, Canada. This article is available for credit. AJR 2016; 207: X/16/ American Roentgen Ray Society Evaluation of T1-Weighted MRI to Detect Intratumoral Hemorrhage Within Papillary Renal Cell Carcinoma as a Feature Differentiating From Angiomyolipoma Without Visible Fat OBJECTIVE. The objective of the present study is to determine whether hemorrhage within papillary renal cell carcinoma (RCC) can be detected using T1-weighted MRI and to ascertain whether it can be used to differentiate papillary RCC from angiomyolipoma (AML) without visible fat. MATERIALS AND METHODS. A retrospective case-control study compared 11 AMLs without visible fat with 58 papillary RCCs smaller than 5 cm that were evaluated using MRI between 2003 and Two blinded radiologists subjectively evaluated MR images to identify the presence of intratumoral hemorrhage on the basis of a decrease in signal intensity (SI) on inphase, compared with opposed-phase, chemical-shift MRI and also on the basis of the SI of the lesion compared with that of the renal cortex on fat-suppressed T1-weighted MRI. A third radiologist established consensus and measured the ratio of the SI of the lesion to that of the renal cortex (hereafter referred to as the SI ratio ) on T2-weighted MRI; the SI loss index, as calculated using the equation [(SI tumorip SI tumorop ) / SI tumorop ] 100, where IP denotes the in-phase image and OP denotes the opposed-phase image; and the SI ratio on fat-suppressed T1-weighted MRI. Analyses were performed using tests of association and ROCs. RESULTS. When AMLs without visible fat were compared with papillary RCCs, no statistically significant difference in the T2-weighted SI ratio was noted (p = 0.08). Papillary RCCs had a lower mean (± SD) SI loss index ( 3.7% ± 17.3%; range, 51.3% to 31.3%) than did AMLs without visible fat (37.8% ± 76.1%; range, 15.6% to 184.4%) (p < 0.001). A mean SI loss index of less than 16% resulted in an AUC of 0.71 (95% CI, ), with a sensitivity and specificity of 22.8% and 100%, respectively, for the diagnosis of papillary RCC. After consensus review, none of the AMLs without visible fat and 16 of the 58 papillary RCCs (27.6%) were found to have a decrease in SI on subjective analysis (p = 0.06, κ = 0.60). Between groups, no differences were noted in the SI ratio on fat-suppressed T1-weighted MRI (p = 0.58) or in the SI observed on subjective analysis of fat-suppressed T1-weighted MRI (p = 0.20, κ = 0.48). CONCLUSION. The presence of intratumoral hemorrhage within papillary RCC is a specific feature that differentiates papillary RCCs from AMLs without visible fat. Subjective analysis may be more clinically appropriate than chemical-shift MRI because of limitations in the quantitative measurement of T2* signal with the use of chemical-shift MRI. A ngiomyolipoma (AML) is a benign renal mesenchymal tumor of the perivascular endothelial cell (i.e., a PEComa) [1, 2]. Classic or triphasic AML shows varying amounts of dysmorphic blood vessels, smooth muscle, and adipose tissue, with the detection of intratumoral macroscopic (i.e., gross) fat required for the definitive diagnosis of AML on the basis of imaging findings [3, 4]. A total of 5% of AMLs do not have sufficient amounts of fat to be detected using conventional CT or MRI [5]. These AMLs are referred to as AMLs without visible fat [6]. AMLs without visible fat are commonly resected benign renal neoplasms [7, 8]; therefore, preoperative differentiation of AML without visible fat from renal cell carcinoma (RCC) is desirable. Numerous CT and MRI findings associated with AML without visible fat have been reported [4, 6, 9 19]. Of these findings, low T2-weighted signal intensity (SI) is a characteristic finding because of the abundant smooth muscle content of AML without visible fat [5, 6, 17, 20, 21]. Although the T2-weighted SI of AML without visible fat differs significantly from that of clear AJR:207, September

2 Murray et al. cell RCC [13, 17, 19, 22] (with clear cell tumors rarely noted as being hypointense on T2-weighted MRI [23 26]), low T2-weighted SI is commonly observed in papillary RCC [25 28]. Therefore, T2-weighted MRI cannot be used alone to differentiate AML without visible fat from RCC because of substantial overlap with papillary tumors. Multivariate analysis of MRI findings has been reported to improve differentiation of AML without visible fat from papillary RCC [17, 19, 22]. For example, a decrease in SI on opposed-phase T1-weighted chemical-shift MRI noted in combination with hypointensity on T2-weighted MRI is specific for AMLs without visible fat because, although papillary RCCs may also show a decrease in SI on opposed-phase images, these papillary tumors have a prolonged T2 signal [6, 17, 19, 22, 29]. Unfortunately, despite preliminary reports of the usefulness of chemical-shift MRI in the detection of microscopic fat in AMLs without visible fat [10], it is now known that few AMLs without visible fat have sufficient amounts of fat to be detected using chemical-shift MRI [6, 18, 22]. Moreover, although the combination of rapid wash-in enhancement with washout kinetics on gadoliniumenhanced MRI and low T2-weighted SI may differentiate AML without visible fat from papillary RCC (with the latter characteristically showing progressive enhancement) [17, 22], approximately one-quarter of AMLs without visible fat may not show this typical enhancement pattern [6, 30]. Unlike classic AML, which may present with spontaneous hemorrhage (with increased risk of hemorrhage occurring in AMLs > 4 cm) [31 33], AMLs without visible fat do not, to our knowledge, present with hemorrhage; are predominantly composed of smooth muscle [5, 6]; and are typically discovered incidentally when sporadic. Conversely, on histopathologic analysis, RCCs commonly show internal hemorrhage, and of the various RCC subtypes, papillary RCC most frequently shows intratumoral hemorrhage [34, 35]. Yoshimitsu et al. [36] first reported the use of chemical-shift MRI (i.e., detection of susceptibility artifact on the longer-te in-phase image, compared with the shorter-te opposed-phase image) as a finding associated with RCC and, in particular, with papillary RCC [36]. More recently, this finding was reevaluated by Childs et al. [37], who also concluded that this finding was specific for RCC and that it was more common in papillary tumors, with histologic analysis confirming its association with the presence of intratumoral hemorrhage. The purpose of the present study is to evaluate whether intratumoral hemorrhage within papillary RCC, as detected using qualitative and quantitative analysis of A C chemical-shift MRI and T1-weighted fatsuppressed MRI, which is an additional hemorrhage-sensitive sequence [38], can be used to differentiate papillary RCC from AMLs without visible fat. Intratumoral hemorrhage may be an additional discriminating imaging feature to help further characterize solid renal masses with a low T2-weighted SI. Materials and Methods Patients This retrospective study was approved by the institutional review board at The Ottawa Hospital, The University of Ottawa, which waived the need for informed consent. We searched the pathology department and PACS databases at our institution to identify patients with histologic diagnoses of papillary RCC (on the basis of findings from either surgical resection or 18-gauge core biopsy) who underwent MRI between May 2003 and October A total of 69 patients with 76 papillary RCCs were identified. Papillary RCCs included in the study were required to be less than or equal to 5 cm (because tumors > 5 cm are more likely to be malignant and managed surgically [39]) and solid (i.e., not cystic or necrotic). Sixteen of the 69 patients with papillary RCC were excluded from the study; of these 16 patients, 10 had RCCs larger than 5 cm, four had primarily cystic RCCs, one patient had an incomplete MRI examination, and one patient had severe motion artifact on the MR image, which precluded Fig year-old man with right anterior interpolar region papillary renal cell carcinoma. A C, Axial T2-weighted single-shot turbo spin-echo (A), in-phase (B), and opposed-phase (C) T1-weighted gradient-recalled echo MR images each show tumor (arrow). Tumor is heterogeneously hypointense to renal cortex on T2-weighted image (arrow, A). Peripheral foci of decrease in signal intensity (arrowheads, B) on in-phase images, compared with opposed-phase images, were identified by both readers. Signal intensity loss index was 8.0%. B 586 AJR:207, September 2016

3 Detection of Intratumoral Hemorrhage Within Papillary RCC on T1-Weighted MRI TABLE 1: Pulse Sequence Parameters Chemical-Shift T1-Weighted GRE T2-Weighted TSE/FSE Volume-Interpolated T1-Weighted 3D GRE a 3D GRE Single-Shot TSE/FSE 3 T 1.5 T TSE/FSE 3 T 1.5 T 2D GRE Pulse Sequence Breath-hold Breath-hold Breath-hold Physiologic parameter Breath-hold Breath-hold Breath-hold Respiratory triggered Duration (s) Chemical or spectral inversion recovery Fat suppression NA NA NA NA NA Chemical or spectral inversion recovery 5000/ / / /1.4 In phase, 7.6/4.6; opposed phase, 7.6/2.3 In phase, 5.5/2.5; opposed phase, 5.5/1.3; in phase, 4.0/2.2; opposed phase, 4.0/1.1 TR/TE In phase, /4.6; opposed phase, /2.3 Flip angle ( ) Bandwidth (Hz) No. of excitations Half-Fourier 1 1 Acceleration factor Matrix size 256/ / / / FOV (cm) Slice thickness (mm) Note Imaging was performed using a clinical 1.5-T MRI system (Magnetom Avanto [Siemens Healthcare] or Achieva [Philips Healthcare]) or a 3-T MRI system (Magnetom Trio [Siemens Healthcare] or Discovery 750 W [GE Healthcare]). GRE = gradient-recalled echo, TSE = turbo spin echo, FSE = fast spin echo, NA = not applicable. a Volumetric interpolated breath-hold examination (VIBE, Siemens Healthcare), LAVA (GE Healthcare), or THRIVE (Philips Healthcare). assessment. Three of the 53 remaining patients had multiple tumors, with two RCCs noted in one patient and four RCCs noted in two patients. Each of the two patients with four RCCs had one tumor excluded from evaluation because the tumor was larger than 5 cm. The final cohort with papillary RCC, therefore, included 53 patients with 58 papillary RCCs. To establish a comparison group of AMLs without visible fat diagnosed during the same period when the 58 papillary RCCs were diagnosed, we added one patient with AML without visible fat who underwent MRI to an existing database of 10 patients with AML without visible fat who underwent MRI. The comparison group therefore included 11 patients with 11 AMLs without visible fat. Ten of the 11 AMLs without visible fat and all 58 papillary RCCs in our cohort had previously been studied [6, 22, 29]; however, the objective of the present study (i.e., to detect the presence of intratumoral hemorrhage on chemical-shift and fat-suppressed T1-weighted MRI) had not been the focus of the previous investigations. Data on patient age at diagnosis, sex, and the location of the renal lesion were recorded. Histopathologic diagnoses of both AML and papillary RCC were independently verified by a genitourinary pathologist with 11 years of experience. For four lesions (one AML without visible fat and three papillary RCCs), histopathologic diagnosis was made by analyzing lesion specimens obtained during 18-gauge core needle biopsy. For all other tumors, histopathologic analysis involved evaluation of specimens obtained during partial or total nephrectomy. The lesion characteristics used in the histopathologic diagnosis of papillary RCC and AML have been described elsewhere [6, 40 42]. We did not reevaluate the papillary RCCs for the presence of intratumoral hemorrhage at the time of histopathologic analysis because this finding had been validated repeatedly elsewhere [23, 34, 36, 37]. MRI Technique Fifty-five of the 64 patients in the groups with papillary RCCs or AMLs without visible fat underwent MRI examination conducted at our institution. MRI was performed using one of three clinical 1.5-T (Magnetom Symphony, Siemens Healthcare) or 3-T systems (Magnetom Trio, Siemens Healthcare; and Discovery 750 W, GE Healthcare) with the use of a torso phased-array coil. For all patients, the following pulse sequences were performed: axial breath-hold in-phase and opposed-phase T1-weighted gradient-recalled echo (GRE), axial respiratory-triggered or breathhold T2-weighted turbo spin-echo/fast spin-echo (TSE/FSE), and breath-hold fat-suppressed T1-weighted 3D volume-interpolated GRE sequences. For the T1-weighted dual-echo GRE sequence, imaging was performed as 2D (n = 35 patients) or 3D (n = 20) acquisition. Before 2006, respiratory-triggered T2-weighted TSE sequences were performed (n = 22); however, after 2006, breath-hold singleshot T2-weighted TSE sequences were performed (n = 33). All patients had breath-hold fat-suppressed T1-weighted 3D volumeinterpolated GRE sequences performed. The pulse sequence parameters for chemical-shift T1-weighted (both in-phase and opposed-phase) GRE, T2-weighted TSE/FSE, and fat-suppressed T1-weighted volume-interpolated GRE sequences performed on 1.5-T and 3-T MRI systems are shown in Table 1. AJR:207, September

4 Murray et al. TABLE 2: Quantitative MRI Parameters of Angiomyolipoma (AML) Without Visible Fat and Papillary Renal Cell Carcinoma (RCC) Tumor SI Loss Index a (%) T1-Weighted SI Ratio b T2-Weighted SI Ratio c AML without visible fat 37.8 ± 76.1 ( 15.6 to 184.4) 0.85 ± 0.2 ( ) 0.64 ± 0.1 ( ) Papillary RCC 3.7 ± 17.3 ( 51.3 to 31.3) 0.90 ± 0.26 ( ) 0.78 ± 0.25 ( ) p d < Note Except for p values, data are mean ± SD (range). The signal intensity (SI) ratio was defined as the ratio of the SI of the lesion to that of the renal cortex. a [(SI tumorip SI tumorop ) / SI tumorop ] 100, where IP denotes in-phase images and OP denotes opposed-phase images. b T1-weighted SI tumor / T1-weighted SI renalcortex. c T2-weighted SI tumor / T2-weighted SI renalcortex. d Independent t tests with a Bonferroni correction of 3. The remaining nine patients underwent MRI examinations performed at peripheral institutions, with studies available for review through the PACS at our institution. MRI was performed using clinical 1.5-T systems (with Magnetom Avanto [Siemens Healthcare] used for three patients and Achieva [Philips Healthcare] used for six patients.) The MRI technique used was similar to that used at our institution and involved the use of similar sequence parameters, as shown in Table 1. The following sequences were performed for all nine patients: breath-hold 2D T1-weighted dual-echo GRE, breath-hold T2-weighted singleshot TSE, and breath-hold fat-suppressed volumeinterpolated 3D T1-weighted GRE. Subjective Analysis Two blinded abdominal radiologists with 10 and 16 years of experience in genitourinary imaging evaluated the lesions on chemical-shift and fat-suppressed T1-weighted MRI. Radiologists were provided with information on lesion location only. Studies were reviewed using a PACS workstation (Horizon Medical Imaging, version 11.9; McKesson). Both radiologists were instructed to look for a focal or diffuse decrease in SI on longer-te in-phase images, compared with opposedphase images, and to record whether the finding was present or absent as a binary outcome (Fig. 1). Similarly, both radiologists assessed fat-suppressed T1-weighted MR images to determine the subjective SI of the lesion relative to the renal cortex using a 3-point scale, where the lesion could be hypointense, isointense, or hyperintense to the renal cortex. A third abdominal radiologist with 11 years of experience in genitourinary imaging established the consensus diagnosis for cases with discordant diagnoses. Quantitative Analysis The third radiologist also evaluated the lesions quantitatively by performing ROI analyses on T2-weighted chemical-shift MR images and fatsuppressed T1-weighted MR images. An ROI was placed in the midpoint of the lesion, encompassing up to two-thirds of the tumor on all sequences at the same level. A fixed-diameter (5 mm) ROI was also placed in the ipsilateral renal cortex when SI ratios were calculated, as described elsewhere [17]. The SI ratios on T2-weighted and fat-suppressed T1-weighted MR images were calculated using the following equation: SI tumor / SI cortex [17]. For chemical-shift MRI, the SI loss index was calculated as described elsewhere [37], with the use of the following equation: [(SI tumorip SI tumorop ) / SI tumorop ] 100, where IP denotes the in-phase image and OP denotes the opposed-phase image. The greater the decrease in SI on in-phase images versus opposed-phase images, the more negative the value of the SI loss index was likely to be. The expected loss of SI related to the longer TE of the in-phase sequence was considered negligible in the present study, as has been reported in previously published studies [36, 37]. Standardized ROI placement was used, rather than measurement of areas of a visible decrease in SI, to determine whether there is any additional benefit of quantitative versus subjective analysis. Statistical Analysis Parametric data, presented as mean (± SD) values, were compared using independent t tests, and subjective data were compared using the chisquare test of proportions, with interobserver agreement assessed using the Cohen kappa statistic. A Bonferroni correction was applied to correct for familywise error. To determine the diagnostic accuracy of each MRI finding for papillary RCCs and AMLs without visible fat, ROC curves were generated for statistically significant variables and the AUC was calculated. The optimal sensitivity and specificity were recorded using the Youden J statistic. The threshold value p < 0.05 (unless Bonferroni correction was applied) indicated a statistically significant difference. Statistical analysis was performed using Stata data analysis and statistical software (version 13, StataCorp). Results No difference in mean patient age was noted when AMLs without visible fat and papillary RCCs were compared (57.3 ± 4.9 vs 62.2 ± 10.9 years; p = 0.20). More women had AMLs without visible fat (90.9%; 10/11 patients) than papillary RCCs (33.9%; 18/53 patients) (p = 0.001). The mean size of AMLs without visible fat was smaller than that of papillary RCCs 12.8 ± 4.4 vs 25.3 ± 9.7 mm; p < 0.001). Findings of quantitative imaging analysis are presented in Table 2. No statistically significant difference in the T2-weighted SI ratio was noted when AML without visible fat was compared with papillary RCC (p = 0.08). Papillary RCCs had a lower mean SI loss index ( 3.7% ± 17.3%; range, 51.3% to 31.3%) than did AMLs without visible fat (37.8% ± 76.1%; range, 15.6% to 184.4%) (p < 0.001) (Fig. 2). No AMLs without visible fat had an SI loss index lower than 16%; however, this degree of SI loss was only present in 20.7% of papillary RCCs (12/58). For the diagnosis of papillary RCC, an SI loss index of less than 16% had an AUC of 0.71 (95% CI, ), sensitivity of 22.8%, and specificity of 100% (Fig. 3). The first reader identified one AML without visible fat for which a subjectively assessed decrease in SI was noted on in-phase versus opposed-phase images, whereas the second reader was unable to identify any AMLs without visible fat that showed a subjective decrease in SI on in-phase images, compared with opposed-phase images. After consensus review, zero of 11 AMLs without visible fat and 16 of 58 papillary RCCs (27.6%) showed a decrease in SI on in-phase images compared with opposed-phase images, with moderate interobserver agreement (κ = 0.60). Subjective analysis of chemicalshift MRI identified an additional 10 papillary tumors with a decrease in SI that did not show a quantitative SI loss index of less than 16% (Fig. 1). Conversely, quantitative analysis identified six papillary RCCs that had an SI loss index of less than 16% and that were not subjectively considered to show a decrease in SI on visual analysis. Combining a subjective decrease in SI and a quantitative 588 AJR:207, September 2016

5 Detection of Intratumoral Hemorrhage Within Papillary RCC on T1-Weighted MRI (i.e., less than 16%) loss in SI improved the sensitivity for the diagnosis of papillary RCC, resulting in a sensitivity of 37.9% (95% CI, %) and a specificity of 100% (95% CI, %). Of the 58 papillary RCCs evaluated, a total of 37.9% (n = 22) showed a decrease in SI on in-phase chemical shift MRI, 10.3% (n = 6) showed a decrease in SI on subjective and quantitative analysis, 10.3% (n = 6) showed a decrease in SI on quantitative analysis only, and 17.2% (n = 10) showed a decrease in SI on visual analysis only. No statistically significant difference in the SI ratio on fat-suppressed T1-weighted MRI was noted when AML without visible fat was compared with papillary RCC (p = 0.58). In addition, no statistically significant difference in subjective SI assessment on fatsuppressed T1-weighted MRI was noted by either reader when AML without visible fat was compared with papillary RCC, and interobserver agreement was weak (p = 0.20, κ = 0.48); however, neither reader considered any AML without visible fat to be hyperintense on T1-weighted MRI. Discussion The present study confirms that intratumoral hemorrhage within papillary RCC can be detected using chemical-shift MRI and illustrates that this imaging finding may be used as an additional feature with which to further characterize solid T2-hypointense renal masses and differentiate papillary RCC from AMLs without visible fat. In our study, a qualitative or quantitative decrease in SI on in-phase versus opposed-phase chemicalshift MRI was specific for the diagnosis of papillary RCC but was not noted in AMLs without visible fat. These results are important because when a small enhancing T2-hypointense renal mass is seen in clinical practice, differentiating between papillary RCC and AML without visible fat is often challenging, and additional discriminating features, such as microscopic fat and an enhancement pattern, are not always observed. In the present study, no difference in T2-weighted SI was noted when papillary RCC was compared with AML without visible fat, which confirms findings reported elsewhere [5, 6, 17, 20, 21, 25 28]. AMLs without visible fat have an intrinsically low T2 signal because of their smooth muscle content [7]. Unlike clear cell RCC (which is rarely T2 hypointense [23]), papillary RCC characteristically shows shortened T2 values that are thought to be related to papillary architecture Fig. 2 Box-andwhisker plots comparing quantitative signal intensity loss index associated with renal lesions. Mean signal intensity loss index was lower in papillary renal cell carcinoma (RCC) than in angiomyolipoma without visible fat (p < 0.001), indicating greater signal intensity loss. Threshold signal intensity loss index of less than 16% (dotted line) was specific for papillary RCC. Horizontal lines within boxes denote mean values, vertical lines and whiskers denote 95% CIs, and black circles denote outliers. Fig. 3 ROC curve analysis for diagnosis of papillary renal cell carcinoma, compared with angiomyolipoma without visible fat, using signal intensity loss index threshold of less than 16%. Gray line denotes mean. Signal Intensity Loss Index (%) Sensitivity and intratumoral hemorrhage [23, 36]. Therefore, the main differential diagnosis for an enhancing T2-hypointense renal lesion is papillary RCC and AML without visible fat. The use of multivariate analysis of additional MRI findings (e.g., intratumoral lipid, enhancement pattern, and homogeneity [6, 43]) must be relied on for potential differentiation. These additional findings can be limited because approximately one-quarter of AMLs without visible fat may show gradual progressive enhancement [6, 30], and few AMLs without visible fat have sufficient amounts of microscopic fat to be detected using chemical-shift MRI [6, 18, 22]. Assessment of tumor homogeneity is limited by the subjective nature of the finding and, to our knowledge, has not been quantitatively evaluated with MRI Angiomyolipoma Without Visible Fat Papillary RCC Specificity The present study confirmed that intratumoral hemorrhage can be detected in papillary tumors by observing a decrease in SI on the longer-te in-phase image, compared with the shorter-te opposed-phase images. The rate of the decrease in the SI observed in papillary RCCs in the present study compares favorably with the rates described by Yoshimitsu et al. [36] and Childs et al. [37], with approximately 40% of papillary tumors showing the finding. In our study, an SI loss index of less than 16% was specific for papillary RCC and identified an additional six tumors that did not show a visual decrease in SI on subjective analysis. This finding compares favorably to the results from the study by Yoshimitsu et al. The use of quantitative MRI analysis of dual-echo chemical-shift AJR:207, September

6 Murray et al. MRI to measure T2* effects in renal masses should be interpreted and applied cautiously because of differences that can be expected in relation to various factors, including primarily field strength, TR, and TE [44]. Although the quantitative results of our study using the previously described SI loss index are concordant with those previously published by Yoshimitsu et al. [36] and Childs et al. [37], if quantitative measurement of T2* in renal masses is to be applied in clinical practice, it may be better performed using a dedicated T2* GRE sequence with the use of a body coil at specified field strengths, to control for differences that would be expected because of hardware and pulse sequence acquisition parameters as well as because of confounding effects related to T1 signal and the presence of microscopic fat or intracellular lipid [45, 46]. Nevertheless, the subjective evaluation of dual-echo chemical-shift MRI for susceptibility effects in renal masses can be readily applied in clinical practice, and more sensitive techniques for the detection of internal hemorrhage, such as susceptibility weighted MRI, may be of additional benefit [47, 48]. Further analysis is required. In the present study, fat-suppressed T1-weighted imaging was not useful in differentiating papillary RCC from AML without visible fat. This may be related to the nature of the intratumoral hemorrhage within papillary tumors, which usually is in the form of hemosiderin [34, 35]. Hemosiderin would be expected to show low T1-weighted SI, whereas deoxyhemoglobin is typically hyperintense on T1-weighted MRI [49]. In the present study, no AML without visible fat was considered hyperintense on T1-weighted MRI, which is a finding that is concordant with results of a previous study by Hindman et al. [13], which compared AML without visible fat with clear cell RCC and which found that no AML without visible fat showed internal hemorrhage on fatsuppressed T1-weighted MRI. There are limitations to the present study. To maximize our sample size, we used a long study period, which resulted in heterogeneity in MRI protocols; however, our study design and the MRI techniques used are comparable to what has been previously reported. Despite the long study period, the number of AMLs without visible fat remained relatively small, and our results require validation in future studies. Including patients with multiple lesions in the group with papillary RCC introduces cluster bias into our study; however, we think that this is a minor limitation because only three patients had multiple RCCs. We did not assess the use of chemical-shift MRI for the detection of intratumoral lipid in AMLs without visible fat or papillary RCC tumors because this has been previously reported elsewhere [22, 29]. Similarly, we did not assess other MRI features that may differentiate papillary RCC from AML without visible fat (e.g., contrast enhancement characteristics, DWI, or heterogeneity) because these features have also been previously reported [22, 29, 43, 50] and were not the intended focus of the study. In conclusion, intratumoral hemorrhage within papillary RCC can be detected using qualitative or quantitative analysis of chemical-shift MRI, by noting a decrease in SI when longer-te in-phase images are compared with shorter-te opposed-phase images. Although sensitivity was low, this imaging finding was not observed in AMLs without visible fat, showing high specificity for papillary tumors. Our results suggest that intratumoral hemorrhage, when detected using chemical-shift MRI, can be used as an additional discriminating imaging feature in the characterization of solid T2-hypointense renal masses. 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