Davide Ippolito

Hepatocellular carcinoma in cirrhotic liver disease: functional computed tomography with perfusion imaging in the assessment of tumor vascularization

RATIONALE AND OBJECTIVES Our goal was to prospectively determine the value of perfusion computed tomography (CT) in the quantitative assessment of tumor-related angiogenesis in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Forty-seven patients met all the following inclusion criteria: 1) Child-Pugh class A or B liver cirrhosis; 2) presence of a single lesion suspected as HCC at screening ultrasound examination; and 3) lesion diameter between 1 and 3 cm. All patients underwent contrast-enhanced ultrasound, pre- and post-contrast triple-phase CT, and perfusion computed tomographic study using multidetector 16-slice CT. Six parameters related to the blood microcirculation and tissue perfusion were measured for the focal liver lesion and cirrhotic parenchyma: perfusion (P), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution; univariate paired and unpaired Wilcoxon signed rank tests were used for statistical analysis. RESULTS HCC was diagnosed in 21 of the 47 patients; in the remaining 26, HCC was not found at contrast-enhanced ultrasound and multidetector 16-slice computed tomographic study. The values of perfusion parameters measured within tumor tissue were: P (ml/s/100 g): median = 47.0 (first quartile = 36.0, third quartile = 61.4); BV (ml/100 mg): median = 24.0 (first quartile = 18.7, third quartile = 29.3); HPI (%): median = 78.4 (first quartile = 62.9, third quartile = 100); AP (ml/min): median = 45.9 (first quartile = 39.0, third quartile = 60.1); PP (ml/min): median = 9.0 (first quartile = 0.0, third quartile = 24.5); and TTP (seconds): median = 18.7 (first quartile = 16.3, third quartile = 26.5). The corresponding values calculated in cirrhotic surrounding parenchyma were P (ml/s/100 g): median = 11.5 (first quartile = 9.4, third quartile = 13.9); BV (ml/100 mg): median = 10.7 (first quartile = 7.1, third quartile = 14.2); HPI (%): median = 10.6 (first quartile = 8.7, third quartile = 11.9); AP (ml/min): median = 13.2 (first quartile = 10.1, third quartile = 15.5); PP (ml/min) median = 55.2 (first quartile = 40.1, third quartile = 79.5); and TTP (seconds): median = 41.7 (first quartile = 38.9, third quartile = 44.6). P, BV, HPI, and AP values were higher (P < .001), whereas PP and TTP were lower (P < .001) in HCC relative to the surrounding liver. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different (P > .001). CONCLUSION In cirrhotic patients with HCC, perfusion computed tomographic technique can provide quantitative information about tumor-related angiogenesis.

Perfusion CT in cirrhotic patients with early stage hepatocellular carcinoma: Assessment of tumor-related vascularization

PURPOSE To assess the value of CT-perfusion in determining the quantitative vascularization features of early hepatocellular carcinoma (HCC) in cirrhotic patients. MATERIALS AND METHODS A total of 35 cirrhotic patients with single histologically proven HCC not exceeding 3cm in diameter underwent conventional triple-phase multidetector computed tomography (MDCT) examination. All patients were also examined with CT-perfusion (CTp) technique after i.v. injection of 50mL of iodinated contrast. Data were analyzed using a dedicated software which generated a quantitative map of liver parenchyma perfusion. The following parameters were assessed: hepatic perfusion (HP); blood volume (BV); arterial perfusion (AP); time to peak (TTP) and hepatic perfusion index (HPI). Univariate Wilcoxon signed rank test was used for statistical analysis. RESULTS In the 35 HCCs evaluated, the following quantitative data were obtained: HP (mL/s/100g): median=47.0 (1(st)qt=35.5; 3(st)qt=61.2); BV (mL/100mg): median=22.5 (1(st)qt=18.4; 3(st)qt=27.7); AP (mL/min): median=42.9 (1(st)qt=35.8; 3(st)qt=55.6); HPI(%): median=75.3 (1(st)qt=63.1; 3(st)qt=100); TTP(s): median=18.7 (1(st)qt=16.8; 3(st)qt=24.5). Perfusion values calculated in cirrhotic liver parenchyma were HP: median=10.3 (1(st)qt=9.1; 3(st)qt=13.2); BV: median=11.7 (1(st)qt=9.6; 3(st)qt=15.5); AP: median=10.4 (1(st)qt=8.6; 3(st)qt=11.3); HPI: median=17.5 (1(st)qt=14.3; 3(st)qt=19.7); TTP: median=44.6 (1(st)qt=40.3; 3(st)qt=50.1). HP, BV, HPI and AP were found to be significantly higher in HCC lesion than in liver parenchyma (p<0.001), while TTP was significantly lower (p<0.001). CONCLUSION CT-perfusion technique allows obtaining quantitative information about tumor-related vascularization of early HCC, in patients with liver cirrhosis.

Quantitative evaluation of CT-perfusion map as indicator of tumor response to transarterial chemoembolization and radiofrequency ablation in HCC patients.

PURPOSE To assess if radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may influence the evaluation of perfusion parameters obtained with CT-perfusion (CT-p) in HCC treated patients. MATERIALS AND METHODS Thirty-three consecutive cirrhotic patients with biopsy-proven diagnosis of HCC lesions and candidates to TACE or RFA were included. The CT-p study of hepatic parenchyma and of treated lesions was performed about 1 month after treatment on 16 multidetector CT after injection of 50mL of non ionic contrast agent (350mg I/mL) at a flow rate of 6mL/s acquiring 40 dynamic scans. A dedicated perfusion software which generated a quantitative map of arterial and portal perfusion by means of colour scale was employed.The following perfusion parameters were assessed before and after RFA or TACE treatment: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), time to peak (TTP), hepatic perfusion index (HPI). RESULTS A complete treatment was obtained in 16 cases and incomplete treatment in the 17 remaining cases. The perfusion data of completely treated lesions were: HP 10.2±6.3; AP 10.4±7; BV 4.05±4.8; TTP 38.9±4.2; HPI 9.9±9.2, whereas in partially treated lesions were: HP 43.2±15.1mL/s/100g; AP 38.7±8.8mL/min; BV 20.7±9.5mL/100mg; TTP 24±3.7s; HPI 61.7±7.5%. In adjacent cirrhotic parenchyma, the parameters of all evaluated patients were: HP 13.2±4; AP 12.3±3.4; BV 11.8±2.8; TTP 43.9±2.9; and HPI 17.1±9.8. A significant difference (P<0.001) was found for all parameters between residual viable tumor tissue (P<0.001) compared to successfully treated lesion due to the presence of residual arterial vascular structure in viable portion of treated HCC. CONCLUSION According to our results, CT-p evaluation is not influenced by TACE or RFA treatments, thus representing a feasible technique that allows a reproducible quantitative evaluation of treatment response in HCC patients.

Perfusion computed tomographic assessment of early hepatocellular carcinoma in cirrhotic liver disease: initial observations

Objective: To prospectively assess perfusion computed tomography (CT) for evaluation of tumor vascularity of early hepatocellular carcinoma (HCC) in patients with cirrhosis. Methods: The study cohort included 30 patients who had Child-Pugh class A or B liver cirrhosis and a single histopathologically confirmed HCC not exceeding 3 cm in diameter. All patients underwent perfusion CT study using a multidetector 16-slice CT. Four perfusion parameters were measured for the HCCs and cirrhotic liver parenchyma: hepatic perfusion (HP), blood volume (BV), arterial perfusion (AP), and time to peak (TTP). Perfusion parameters were described with quartile (qt) values of their distribution; univariate paired Wilcoxon signed rank test was used for statistical analysis. Results: The values of perfusion parameters measured within tumor tissue were the following: HP (milliliters per 100 g per minute): median = 45.7 (first qt = 35.3; third qt = 61.3); BV (milliliters per 100 mg): median = 20.6 (first qt = 13.0; third qt = 27.6); AP (milliliters per minute): median = 44.2 (first qt = 36.7; third qt = 57.0); TTP (seconds): median = 18.7 (first q = 15.9; third qt = 24.0). Our data showed that HP, BV, and AP values were higher (P < 0.001), whereas TTP was lower (P < 0.001), in HCCs relative to the cirrhotic liver parenchyma. For all the CT perfusion parameters calculated, there was a significant difference between HCC and background cirrhotic liver. Conclusions: Preliminary results suggest that in patients with cirrhosis and early HCC, perfusion CT is a feasible technique for noninvasive assessment of tumor vascularity.

Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM)

PURPOSE To assess the role of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of patients with suspicion of multiple myeloma (MM). MATERIALS AND METHODS A total of 138 patients (76 male and 62 female; mean age 63.5 years, range 50-81 years), with early MM, underwent WBLDCT protocol study, performed on 16-slice scanner (Brilliance, Philips Medical System, Eindhoven, The Netherlands): tube voltage 120 kV; tube current time product 40 mAs. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done by using multiplanar reformatted images. The overall dose delivered to each patient was 4.2 mSv. Every patient gave personal informed consent, as required by our institution guidelines. RESULTS The diagnosis was established either by histopathology or imaging follow-up (size increase of over a period time). In all 138 patients, image resolution was diagnostic, enabling correct classification of multiple myeloma patients. WBLDCT showed a total of 328 pathologic bone findings in 81/138 patients. CT scanning resulted in complete evaluation of the bone lesions in these areas of the skeleton: skull (42), humerus (15), femur (20), ribs (7), scapulae (13), pelvis (35), clavicle (13), sternum (10), cervical (39), dorsal (65), lombar (48) and sacral rachis (21). In 40/81 bone involvement detected by CT was the only CRAB criterion present. Furthermore, WBLDCT demonstrated pleuro-pulmonary lesions in 20 patients (11 infective, 9 as MM localizations) and 1 renal neoplasia. CONCLUSION WBLDCT, detecting bone marrow localizations and demonstrating extra-osseous findings, with a fast scanning time and high resolution images, is a reliable imaging-based tool for a proper management of MM patients.

Low kV settings CT angiography (CTA) with low dose contrast medium volume protocol in the assessment of thoracic and abdominal aorta disease: a feasibility study

OBJECTIVE To assess the diagnostic quality of low dose (100 kV) CT angiography (CTA), by using ultra-low contrast medium volume (30 ml), for thoracic and abdominal aorta evaluation. METHODS 67 patients with thoracic or abdominal vascular disease underwent multidetector CT study using a 256 slice scanner, with low dose radiation protocol (automated tube current modulation, 100 kV) and low contrast medium volume (30 ml; 4 ml s(-1)). Density measurements were performed on ascending, arch, descending thoracic aorta, anonymous branch, abdominal aorta, and renal and common iliac arteries. Radiation dose exposure [dose-length product (DLP)] was calculated. A control group of 35 patients with thoracic or abdominal vascular disease were evaluated with standard CTA protocol (automated tube current modulation, 120 kV; contrast medium, 80 ml). RESULTS In all patients, we correctly visualized and evaluated main branches of the thoracic and abdominal aorta. No difference in density measurements was achieved between low tube voltage protocol (mean attenuation value of thoracic aorta, 304 HU; abdominal, 343 HU; renal arteries, 331 HU) and control group (mean attenuation value of thoracic aorta, 320 HU; abdominal, 339; renal arteries, 303 HU). Radiation dose exposure in low tube voltage protocol was significantly different between thoracic and abdominal low tube voltage studies (490 and 324 DLP, respectively) and the control group (thoracic DLP, 1032; abdomen, DLP 1078). CONCLUSION Low-tube-voltage protocol may provide a diagnostic performance comparable with that of the standard protocol, decreasing radiation dose exposure and contrast material volume amount. ADVANCES IN KNOWLEDGE Low-tube-voltage-setting protocol combined with ultra-low contrast agent volume (30 ml), by using new multidetector-row CT scanners, represents a feasible diagnostic tool to significantly reduce the radiation dose delivered to patients and to preserve renal function, while also maintaining adequate diagnostic quality images in assessment of aorta.

Preoperative Computed Tomography to Predict and Stratify the Risk of Severe Pancreatic Fistula After Pancreatoduodenectomy

Abstract The aim of this article is to assess whether measures of abdominal fat distribution, visceral density, and antropometric parameters obtained from computed tomography (CT) may predict postoperative pancreatic fistula (POPF) occurrence. We analyzed 117 patients who underwent pancreatoduodenectomy (PD) and had a preoperative CT scan as staging in our center. CT images were processed to obtain measures of total fat volume (TFV), visceral fat volume (VFV), density of spleen, and pancreas, and diameter of pancreatic duct. The predictive ability of each parameter was investigated by receiver-operating characteristic (ROC) curves methodology and assessing optimal cutoff thresholds. A stepwise selection method was used to determine the best predictive model. Clinically relevant (grades B and C) POPF occurred in 24 patients (20.5%). Areas under ROC-curves showed that none of the parameters was per se significantly predictive. The multivariate analysis revealed that a VFV >2334 cm3, TFV >4408 cm3, pancreas/spleen density ratio <0.707, and pancreatic duct diameter <5 mm were predictive of POPF. The risk of POPF progressively increased with the number of factors involved and age. It is possible to deduce objective information on the risk of POPF from a simple and routine preoperative radiologic workup.

Apparent Diffusion Coefficient Maps Integrated in Whole-Body MRI Examination for the Evaluation of Tumor Response to Chemotherapy in Patients with Multiple Myeloma

RATIONALE AND OBJECTIVES To determine the diagnostic value of apparent diffusion coefficient (ADC) maps in the assessment of response to chemotherapy in patients with multiple myeloma (MM). MATERIALS AND METHODS Fourteen patients (seven women) with MM underwent whole-body magnetic resonance imaging (WB-MRI) study on a 1.5T scanner, before and after chemotherapy. DWI with background body signal suppression (DWIBS) sequences (b values: 0, 500, and 1000 mm(2)/sec) were qualitatively analyzed, along with T1 turbo spine echo and short tau inversion recovery T2-weighted images, to evaluate bone lesions. On ADC maps, regions of interest were manually drawn along contours of lesions. The ADC values percentage variation (ΔADC) before (MR1) and after (MR2) chemotherapy were calculated and compared between responders (11 of 14) and nonresponders (3 of 14). The percentage of plasma cells by the means of the bone marrow aspirate was evaluated as parameter for response to chemotherapy. RESULTS Twenty-four lesions, hyperintense on DWIBS as compared to normal bone marrow, were evaluated. In responder group, the mean ADC values were 0.63 ± 0.24 × 10(-3) mm(2)/s on MR1 and 1.04 ± 0.46 × 10(-3) mm(2)/s on MR2; partial or complete signal intensity decrease during follow-up on DWIBS was found along with a reduction of plasma cells infiltration in the bone marrow. The mean ADC values for nonresponders were 0.61 ± 0.05 × 10(-3) mm(2)/s on MR1 and 0.69 ± 0.09 × 10(-3) mm(2)/s on MR2. The mean variation of ΔADC in responders (Δ = 66%) was significantly different (P < .05) than in nonresponders (Δ = 15%). CONCLUSIONS WB-MRI with DWIBS sequences, by evaluating posttreatment changes of ADC values, might represent a complementary diagnostic tool in the assessment of response to chemotherapy in MM patients.

Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

AIM To assess the clinical diagnostic value of functional imaging, combining quantitative parameters of apparent diffusion coefficient (ADC) and standardized uptake value (SUV)max, before and after chemo-radiation therapy, in prediction of tumor response of patients with rectal cancer, related to tumor regression grade at histology. METHODS A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study. All patients underwent a whole body (18)FDG positron emission tomography (PET)/computed tomography (CT) scan and a pelvic magnetic resonance (MR) examination including diffusion weighted (DW) imaging for staging (PET1, RM1) and after completion (6.6 wk) of neoadjuvant treatment (PET2, RM2). Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings. The MR scanning, performed on 1.5 T magnet (Philips, Achieva), included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm²/s. On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2. The percentage decrease of SUVmax (ΔSUV) and ADC (ΔADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade (Mandards criteria; TRG1 = complete regression, TRG5 = no regression). RESULTS After completion of therapy, all the patients were submitted to surgery. According to the Mandards criteria, 22 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; 9 tumors were classified as non responders (TRG3, 4 and 5). Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2 (P < 0.001), whereas the mean ADC values was lower in RM1 than RM2 (P < 0.001), with a ΔSUV and ΔADC respectively of 60.2% and 66.8%. The best predictors for TRG response were SUV2 (threshold of 4.4) and ADC2 (1.29 × 10(-3) mm(2)/s) with high sensitivity and specificity. Combining in a single analysis both the obtained median value, the positive predictive value, in predicting the different group category response in related to TRG system, presented R(2) of 0.95. CONCLUSION The functional imaging combining ADC and SUVmax in a single analysis permits to detect changes in cellular tissue structures useful for the assessment of tumour response after the neoadjuvant therapy in rectal cancer, increasing the sensitivity in correct depiction of treatment response than either method alone.

Tumour-related neoangiogenesis: Functional dynamic perfusion computed tomography for diagnosis and treatment efficacy assessment in hepatocellular carcinoma

BACKGROUND Aim of the study was to determine the value of perfusion computed tomography in the quantitative assessment of tumour-related neoangiogenesis for the diagnosis and treatment of hepatocellular carcinoma lesions. METHODS Overall, 47 consecutive patients with cirrhotic liver disease, with a high risk of hepatocellular carcinoma, and undergoing standard surveillance (six-month intervals) were eligible for inclusion in this prospective study; based on Barcelona Clinic Liver Cancer guidelines, 27 patients were enrolled. Perfusion computed tomography was performed in 29 biopsy-proven hepatocellular carcinoma lesions before and after treatment with transarterial chemoembolization or radiofrequency ablation. The dynamic study was performed with a 256-slice multidetector-computed tomography scanner; the following parameters were measured: hepatic perfusion, arterial perfusion, blood volume, hepatic perfusion index, and time-to-peak in all patients. RESULTS Hepatocellular carcinoma lesions had the following median perfusion values: perfusion 46.3mL/min/100g; blood volume 20.4mL/100mg; arterial perfusion 42.9mL/min; hepatic perfusion index 92.5%; time to peak 18.7s. Significantly lower perfusion values were obtained in correctly treated lesions or surrounding parenchyma than in viable hepatocellular carcinoma tissue. CONCLUSIONS In hepatocellular carcinoma, perfusion computed tomography could contribute to a non-invasive quantification of tumour blood supply related to the formation of new arterial structures, and enable the assessment of therapeutic response.