Transfer learning radiomics based on multimodal ultrasound imaging for staging liver fibrosis.

OBJECTIVES: To propose a transfer learning (TL) radiomics model that efficiently combines the information from gray scale and elastogram ultrasound images for accurate liver fibrosis grading. METHODS: Totally 466 patients undergoing partial hepatectomy were enrolled, including 401 with chronic hepatitis B and 65 without fibrosis pathologically. All patients received elastography and got liver stiffness measurement (LSM) 2-3 days before surgery. We proposed a deep convolutional neural network by TL to analyze images of gray scale modality (GM) and elastogram modality (EM). The TL process was used for liver fibrosis classification by Inception-V3 network which pretrained on ImageNet. The diagnostic performance of TL and non-TL was compared. The value of single modalities, including GM and EM alone, and multimodalities, including GM + LSM and GM + EM, was evaluated and compared with that of LSM and serological indexes. Receiver operating characteristic curve analysis was performed to calculate the optimal area under the curve (AUC) for classifying fibrosis of S4, ≥ S3, and ≥ S2. RESULTS: TL in GM and EM demonstrated higher diagnostic accuracy than non-TL, with significantly higher AUCs (all p < .01). Single-modal GM and EM both performed better than LSM and serum indexes (all p < .001). Multimodal GM + EM was the most accurate prediction model (AUCs are 0.950, 0.932, and 0.930 for classifying S4, ≥ S3, and ≥ S2, respectively) compared with GM + LSM, GM and EM alone, LSM, and biomarkers (all p < .05). CONCLUSIONS: Liver fibrosis can be staged by a transfer learning modal based on the combination of gray scale and elastogram ultrasound images, with excellent performance. KEY POINTS: • Transfer learning consists in applying to a specific deep learning algorithm that pretrained on another relevant problem, expected to reduce the risk of overfitting due to insufficient medical images. • Liver fibrosis can be staged by transfer learning radiomics with excellent performance. • The most accurate prediction model of transfer learning by Inception-V3 network is the combination of gray scale and elastogram ultrasound images.

Differentiation of Renal Tumor Histotypes: Usefulness of Quantitative Analysis of Contrast-Enhanced Ultrasound.

OBJECTIVE: The purpose of this study is to evaluate quantitative analysis of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of renal tumor histotypes. MATERIALS AND METHODS: Between January 2010 and December 2013, 106 clear cell renal cell carcinomas (RCCs) (mean [± SD] diameter, 3.7 ± 1.8 cm), 34 angiomyolipomas (mean diameter, 4.1 ± 1.4 cm), 25 papillary RCCs (mean diameter, 3.5 ± 1.1 cm), and 28 chromophobe RCCs (mean diameter, 2.9 ± 0.9 cm) underwent CEUS quantitative analysis. The dynamic vascular pattern was analyzed with the Fisher exact chi-square test, and rise time, time to peak (TTP), and tumor-to-cortex enhancement ratio were analyzed with the independent-sample t test. RESULTS: Dynamic vascular pattern types I and III (hyperenhancement) were more common among clear cell RCCs, whereas type II (hypoenhancement) was more common among angiomyolipomas, papillary RCCs, and chromophobe RCCs. Irrespective of dynamic vascular pattern class, the rise time and TTP were the shortest in clear cell RCCs and were equal in angiomyolipomas, papillary, and chromophobe RCCs. The tumor-to-cortex enhancement ratio was the highest in clear cell RCCs, was second highest in angiomyolipomas, and was lowest but equal in papillary and chromophobe RCCs. Clear cell RCCs and angiomyolipomas accounted for the majority of the hyperenhancing group. The tumor-to-cortex enhancement ratio of clear cell RCCs was higher than that of angiomyolipomas. With tumor-to-cortex enhancement ratio greater than 146.0% as the cutoff to differentiate clear cell RCC from angiomyolipoma in the hyperenhanced group, the sensitivity and specificity were each 71.4%. In the hypoenhanced group, the tumor-to-cortex enhancement ratio was the same in clear cell RCCs and angiomyolipomas but was higher in papillary and chromophobe RCCs. With tumor-to-cortex enhancement ratio greater than 54.2% as the cutoff point to differentiate clear cell RCCs from papillary and chromophobe RCCs, the sensitivity and specificity were 95.5% and 94.8%, respectively, whereas with a tumor-to-cortex enhancement ratio greater than 57.4% as the cutoff point to differentiate angiomyolipomas from papillary and chromophobe RCCs, the sensitivity and specificity were 90.0% and 96.4%, respectively. CONCLUSION: Quantitative analysis of CEUS can show quantification of enhancement features of different renal tumor histotypes and may be helpful in their differential diagnosis.

Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

PURPOSE: To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. METHODS: Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. RESULTS: No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p < 0.001 for both), homogeneous peak enhancement (100.0% in both EAMLs and TAMLs vs. 43.4% in ccRCCs, p < 0.001 for both), and iso-enhancement in parenchyma phase (53.3% in AMLs, 52.0% in TAMLs vs. 26.5% in ccRCCs, p = 0.034 and 0.013, respectively) were valuable traits for differentiating EAMLs and TAMLs from ccRCCs. Furthermore, with quantitative analysis, RT and TTP were much shorter in ccRCCs than those in EAMLs and TAMLs. However, all these qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p < 0.001), and TOC ratio was much higher in EAMLs (166.01 ± 64.47%) than that in TAMLs (93.74 ± 46.56%)(p < 0.001), though they did make overlaps with ccRCCs. With either heterogeneous peak enhancement or the presence of pseudocapsule or TOC ratio >97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. CONCLUSIONS: Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

Histotype differentiation of hypo-echoic renal tumors on CEUS: usefulness of enhancement homogeneity and intensity.

PURPOSE: The purpose of this study is to evaluate qualitative and quantitative analysis of contrast-enhanced ultrasound (CEUS) in differential diagnoses of hypo-echoic renal tumor histotypes. METHODS: Our study cohort comprised 103 clear cell renal cell carcinomas (ccRCCs), 24 papillary renal cell carcinomas (pRCCs), 28 chromophobe renal cell carcinomas (cRCCs), and 34 angiomyolipomas (AMLs), hypo-echoic on ultrasound, and imaged between January 2011 and December 2013. Enhancement homogeneity and tumor-to-cortex intensity ratio (TOC ratio) were retrospectively analyzed. RESULTS: Overall, heterogeneous enhancement was more common in ccRCCs than AMLs, pRCCs, and cRCCs. TOC ratio showed the trend ccRCC > AML > pRCC = cRCC. Similar trends were seen in tumors <4 cm. Using heterogeneous enhancement or TOC ratio >107.5% to differentiate ccRCC from other histotypes, the sensitivity, specificity, positive and negative predictive values were 93.1%, 74.5%, 84.8%, and 87.5%, respectively. Tumors >4 cm exhibited considerable overlap in enhancement homogeneity among different histotypes. TOC ratios were similar between homo- and heterogeneously enhancing tumors for ccRCCs and for pRCCs and cRCCs, but higher in homogeneously enhancing than heterogeneously enhancing AMLs. In homo- and heterogeneously enhancing tumors, TOC ratios followed the trends ccRCCs > AMLs > pRCCs = cRCCs and ccRCCs > AMLs = pRCCs = cRCCs, respectively. With TOC ratio >105.81% and >72.37% to differentiate homo- and heterogeneously enhancing ccRCCs from other histotypes in tumors >4 cm with same enhancement homogeneity, the sensitivity, specificity, positive and negative predictive values were 70.0%, 85.7%, 70.0%, 85.7%, and 91.7%, 94.4%, 95.7%, 89.5%, respectively. CONCLUSION: CEUS homogeneity and TOC ratio are helpful in differential diagnosis of hypo-echoic renal tumor histotypes. Diameter and enhancement homogeneity should be considered when deciding the diagnostic TOC ratio cutoff.

Dynamic enhancement pattern of intrahepatic cholangiocarcinoma on contrast-enhanced ultrasound: the correlation with cirrhosis and tumor size.

PURPOSE: To retrospectively evaluate the dynamic enhancement pattern of contrast-enhanced ultrasound (CEUS) in intrahepatic cholangiocarcinoma (ICC) of varying sizes and hepatic backgrounds. MATERIALS AND METHODS: CEUS was performed in 98 pathologically confirmed ICCs (n = 39 < 30 mm, n = 59 > 30 mm; n = 45 with cirrhosis and n = 53 with normal liver). The dynamic enhancement pattern of CEUS was retrospectively analyzed. RESULTS: In the arterial phase, heterogeneous hyper-enhancement was more frequent in ICCs with cirrhosis (21/45, 46.7% vs. 11/53, 20.8% in ICCs with normal liver, p = 0.009), while peripheral hyper-enhancement and hypo-enhancement were more common in ICCs with normal liver (14/53, 26.4%; 11/53, 20.8% vs. 2/45, 4.4%; 2/45, 4.4% in ICCs with cirrhosis, p = 0.005 and 0.033, respectively). There were no significant differences between portal and delayed phases. In ICCs < 30 mm, homogeneous hyper-enhancement was more frequently identified (27/39, 69.2% vs. 10/59, 16.9% in ICCs > 30 mm, p < 0.001), whereas in ICCs > 30 mm, heterogeneous, and peripheral hyper-enhancement were more commonly observed (26/59, 44.1% vs. 6/39, 15.4% in ICCs < 30 mm, p = 0.004, and 14/59, 23.7% vs. 2/39, 5.1% in ICCs < 30 mm, p = 0.023, respectively). The washout pattern in portal and delayed phases were not significantly different in ICCs with different sizes. 60.7% (17/28) ICCs < 30 mm and 85.2% (23/27) ICCs > 30 mm with cirrhosis, together with 66.7% (14/21) ICCs < 30 mm with normal liver displayed intense contrast agent uptake (homogeneous or heterogeneous hyper-enhancement) in arterial phase followed by washout in portal and delayed phase, which was much higher than that in ICCs > 30 mm with normal liver (34.4%, 11/32, p < 0.001, <0.001 and =0.027, respectively). CONCLUSION: The CEUS dynamic enhancement pattern of ICC varies with size and hepatic background. The enhancement pattern is indistinguishable from hepatocellular carcinoma on CEUS in most ICCs with cirrhosis and in most ICCs < 30 mm with normal liver.

Contrast-enhanced ultrasonography for evaluation of cystic renal mass: in comparison to contrast-enhanced CT and conventional ultrasound.

PURPOSE: To assess the value of contrast-enhanced ultrasonography (CEUS) in evaluating cystic renal lesions compared with conventional ultrasound (US) and contrast-enhanced computed tomography (CECT). METHODS: One hundred and three patients with complex cystic renal masses underwent preoperative US and CEUS, among which 70 conducted CECT at our institution. The images were analyzed with the number of septa, septa and wall thickness and the presence of solid component, and final diagnosis was made. RESULTS: In malignancies, CEUS demonstrated more septa, thicker wall or septa, and more solid components than US and CECT. CEUS permitted categorization of 51.7% (30/58) and 28.6% (10/35) of malignant tumors in higher grade than by US and CECT, respectively. In benign lesions, CEUS detected more septa than CECT and correctly diagnosed benign cysts which appeared as solid lesions in US. CEUS permitted downgrading of 71.1% (32/45) and 17.1% (6/35) of benign lesions compared to US and CECT. The diagnostic performance of CEUS was better than US for benign cystic lesions. The phenomenon that solid-like component by US did not enhance by CEUS was a strong predictor of benign disease, with a positive predictive value (PPV) of 100%. Enhancement of solid, soft tissue by CEUS was highly predictive of malignancy, with a PPV of 100%. CONCLUSIONS: CEUS was superior to US and CECT in visualizing the number of septa septa and wall thickness, and the presence of solid component of cystic renal lesions. CEUS may play a similar role to CECT in the diagnosis of renal cystic lesions, and better than US.

Differentiation of subtypes of renal cell carcinoma with contrast-enhanced ultrasonography.

We aimed to assess the difference of enhancement patterns among the three RCC subtypes with contrast-enhanced ultrasound (CEUS). Two hundreds cases of pathologically proved clear cell renal cell carcinomas (ccRCC), 58 papillary renal cell carcinomas (pRCC) and 51 chromophobe renal cell carcinomas (chRCC) underwent preoperative conventional ultrasound and CEUS. The wash-in and wash-out pattern, peak enhancement degree and homogeneity, and the presence of pseudocapsule were evaluated by two blinded observers respectively. The interreader agreement in the characterization of CEUS features between two observers was good (κ  = 0.649-0.775). Compared with pRCCs and chRCCs, ccRCCs demonstrated higher frequency of simultaneous wash-in pattern, hyperenhancement and heterogeneity with necrotic areas. Most pRCCs and chRCCs manifested hypoenhancement, homogeneity, fast wash-out and presence of pseudocapsule. The only difference we obtained between pRCC and chRCC was the wash-in pattern, with slow wash-in in pRCC and simultaneous wash-in in chRCC. In small lesions with long diameter≤3 cm, the majority of the three subtypes of RCC showed homogeneous enhancement and there was no difference among them. CEUS was a useful method to preoperatively differentiate the ccRCC from non-ccRCC subtypes. There were no distinguishing features identifid on CEUS that allowed reliable differentiation of pRCC from chRCC.

Quantitative evaluation of contrast-enhanced ultrasound for differentiation of renal cell carcinoma subtypes and angiomyolipoma.

PURPOSE: To investigate the value of quantitative parameters of contrast-enhanced ultrasound (CEUS) in the differentiation of subtypes of renal cell carcinoma (RCC) and angiomyolipoma (AML). METHODS: The quantitative characteristics of 341 RCCs and 88 AMLs were analyzed with quantitative software (SonoLiver). Quantitative analysis was conducted in the whole tumor (ROItumor) and the maximum enhanced area of the tumor (ROImax), acquiring the parameters of maximum intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), and area under the curve (AUC), were derived and analyzed. The difference values between ROImax and normal renal cortex (ΔPar.s, including ΔIMAX, ΔRT, ΔTTP, ΔmTT, ΔAUC) were compared among renal histotypes. RESULTS: All time-related parameters (including RT, TTP and mTT) of ROImax were shorter than the corresponding parameters of ROItumor in RCC subtypes (all p<0.05), but made no statistical difference in AMLs (all p>0.05). There were significant differences of all ΔPar.s among RCC subtypes and AML (all p<0.01). ΔIMAX and ΔAUC showed the trend that ccRCC>AML>pRCC=chRCC. ΔTTP showed AML=pRCC=chRCC>ccRCC, ΔRT and ΔmTT showed AML>pRCC=chRCC=ccRCC. ΔmTT could distinguish RCC from AML with the area under the ROC curve (AUC) of 0.86. The AUC of ΔIMAX and ΔAUC was 0.89 and 0.92 vs 0.85 and 0.85 for discriminating between pRCC (or chRCC) and AML vs ccRCC and AML. CONCLUSIONS: Quantitative analysis of CEUS is a useful modality in AML and RCC subtypes' differentiation, by using ΔmTT, ΔIMAX and ΔAUC.

Qualitative and quantitative analysis with contrast-enhanced ultrasonography: diagnosis value in hypoechoic renal angiomyolipoma.

OBJECTIVE: To evaluate the value of enhancement features and quantitative parameters of contrast-enhanced ultrasonography (CEUS) in differentiating solid hypoechoic renal angiomyolipomas (AMLs) from clear cell renal cell carcinomas (ccRCCs). MATERIALS AND METHODS: We analyzed the enhancement features and quantitative parameters of CEUS in 174 hypoechoic renal masses (32 AMLs and 142 ccRCCs) included in the study. RESULTS: Centripetal enhancement pattern was more common in AMLs than in ccRCCs on CEUS (71.9% vs. 23.2%, p < 0.001). At peak enhancement, all AMLs showed homogeneous enhancement (100% in AML, 27.5% in ccRCCs; p < 0.001). Quantitative analysis showed no significant difference between rise time and time to peak. Tumor-to-cortex (TOC) enhancement ratio in AMLs was significantly lower than that in ccRCCs (p < 0.001). The criteria of centripetal enhancement and homogeneous peak enhancement together with TOC ratio < 91.0% used to differentiate hypoechoic AMLs from ccRCCs resulted in a sensitivity and specificity of 68.9% and 95.8%, respectively. CONCLUSION: Both qualitative and quantitative analysis with CEUS are valuable in the differential diagnosis of hypoechoic renal AMLs from ccRCCs.

Papillary renal cell carcinoma and clear cell renal cell carcinoma: Differentiation of distinct histological types with contrast - enhanced ultrasonography.

PURPOSE: Papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC) have different biological behaviours and imaging features. The role of contrast-enhanced ultrasound (CEUS) in differentiating these two carcinoma subtypes has not been comprehensively studied. MATERIALS AND METHODS: Forty-eight patients with 49 pRCC lesions and 153 patients with 156 ccRCC lesions underwent preoperative conventional ultrasound (US) and CEUS. Among them, 91 patients (25 pRCCs and 66 ccRCCs) also underwent preoperative contrast-enhanced computed tomography (CECT) in our hospital. The characteristics of CEUS and CECT images for each patient imaged were analysed by each of two blinded observers. RESULTS: Images for five (5/25, 20%) pRCC patients demonstrated equivocal or no enhancement using CECT, while all lesions were enhanced using CEUS. From CEUS, images of pRCCs, when compared with ccRCC images, demonstrated significantly higher frequencies of slow wash-in (59.2% vs. 5.8%), fast wash-out (87.7% vs. 46.1%), and hypo-enhancement (57.1% vs. 7.1%) patterns, p<0.001, as well as the presence of pseudocapsule (42.9% vs. 23.1%), p=0.007. For lesions with large diameters (> 3 cm), a higher percentage of pRCC images demonstrated homogeneous enhancement compared with ccRCC images. Using the combination of slow wash-in, fast wash-out, and hypoenhancement patterns at peak as criteria to differentiate pRCC from ccRCC, positive and negative predictive value, and sensitivity and specificity were found to be 86.7%, 86.9%, 53.1%, and 97.4%, respectively. CONCLUSIONS: CEUS imaging features of slow-in, fast-out, and hypo-enhancement patterns may be useful for differentiating pRCC and ccRCC. In addition, CEUS may be helpful for diagnosing hypovascular renal lesions that demonstrate equivocal or no enhancement by CECT and, thus, for improving diagnostic confidence.

The value of contrast-enhanced ultrasound (CEUS) in detecting minute renal cell carcinoma.

UNLABELLED: To investigate the value of contrast-enhanced ultrasound (CEUS) in the detection of minute renal cell carcinoma (MRCC) compared to conventional ultrasound (US) and contrast-enhanced computed tomography (CECT). METHODS: Thirty-eight consecutive patients with 38 histopathologically proven MRCCs (≦15 mm) were enrolled in our study. CEUS and CECT were available in 38 and 24 patients, respectively. The features of CEUS were evaluated and compared to conventional ultrasound (US) and CECT. RESULTS: Ten (26.3%) tumors could not be detected by conventional US, while all tumors were detected by CEUS. The features of tumor border, blood flow, and echogenicity had significant difference between conventional US and CEUS (p=0.000, p=0.003, and p=0.012, respectively). The score of visibility of tumors by CEUS was significant higher than that of conventional US. The sensitivity, specificity, and accuracy of conventional US and CEUS in evaluating tumor necrosis were 42.9%, 50%, and 47.4% vs. 85.7%, 95.8%, and 92.1%, respectively. The enhancement features of MRCC including tumor vascularization, homogeneity, and border had no significant difference between CEUS and CECT (all p>0.05). On CEUS, synchronous-in (89.5%), hypervascular (84.2%), and fast-out (71.1%) were the most commonly observed enhancement characteristics for MRCC. CONCLUSION: CEUS performs better in detecting MRCC than conventional US, and it has the same capabilities in reflecting the enhanced features of MRCC as CECT.

Evaluation of renal urothelial carcinoma by contrast-enhanced ultrasonography.

PURPOSE: To observe ultrasonographic features of urothelial carcinoma in renal pelvis and evaluate contrast-enhanced ultrasound (CEUS) in diagnosis. MATERIALS AND METHODS: Fifty-two patients with urothelial carcinoma underwent preoperative conventional US, colour Doppler flow imaging (CDFI) and CEUS. RESULTS: Of 52 total lesions, 41 (78.8%) could be clearly identified by US, and 49 (94.2%) were enhanced by CEUS. Among US-imaged lesions, 39 (95.1%) were solid tumours, and two (4.9%) were mixed solid-cystic; 25 (61.0%) were isoechoic, 11 (26.8%) hypoechoic, and five (12.2%) hyperechoic. Analysis of tumour blood flow by CDFI characterised 17 avascular lesions (41.5% of total), 16 hypovascular (39.0%), and 8 hypervascular (19.5%). The resistance index ranged from 0.65 to 0.88 (mean of 0.71). Enhancement was seen in 49 lesions after injection of SonoVue. A slow enhancement pattern was observed in 36 lesions (73.5%) relative to renal cortex, and 13/49 (26.5%) showed simultaneous enhancement. At peak enhancement, 38 lesions (77.6%) were hypo-enhanced, six (12.2%) iso-enhanced, and five (10.2%) hyper-enhanced. There were 12 lesions with intertumoural necrosis or haemorrhage (24.5%) that were heterogeneously enhanced, and 37 (75.5%) were homogeneously enhanced. A fast washout pattern was observed in 46 lesions (93.9%), synchronous washout in two (4.08%), and slow washout in one (2.04%). CONCLUSIONS: Slow-in, fast-out, and hypo-enhancement properties are associated with renal urothelial carcinoma and may thus have diagnostic value. We found that CEUS is able to identify tumours that are ambiguous by conventional US, and it thus significantly improves the confidence of diagnosis.

Non-invasive assessment of liver fibrosis in a rat model: shear wave elasticity imaging versus real-time elastography.

The purpose of this study was to investigate the diagnostic value of shear wave elasticity imaging (SWEI) and real-time elastography (RTE) in liver fibrosis induced by dimethylnitrosamine (DMN) and to compare the accuracy of these methods. Seventy male Wistar rats given a single intra-peritoneal injection of DMN and 10 control rats given a saline injection underwent SWEI and RTE to determine their shear wave velocity (V(s)) and liver fibrosis (LF) index, respectively. Correlations between V(s) or the LF index and histologic stage of liver fibrosis (S0-S4) were analyzed, and the diagnostic values of the techniques were assessed using a receiver operating characteristic curve. A positive correlation was found between V(s) and stage of liver fibrosis (r = 0.947, p < 0.001) and between LF index and stage (S) of liver fibrosis (r = 0.662, p < 0.001). For Vs, the areas under the receiver operating characteristic curve for the diagnosis of fibrosis, S ≥ S1, S ≥ S2, S ≥ S3 and S = S4, were 0.983, 0.995, 0.999 and 0.964, respectively; for the LF index, the values were 0.871, 0.887, 0.761 and 0.839, respectively (all p < 0.001). Vs and the LF index values in rats with severe inflammatory activity were significantly higher than those in controls (p < 0.001). In conclusion, positive correlations exist between V(s) or the LF index and the severity of liver fibrosis in rats. Vs is more accurate than the LF index in predicting liver fibrosis in rats. However, severe inflammatory activity may reduce the accuracy of both techniques.