Salvatore Francesco Carbone

Diffusion-weighted magnetic resonance imaging in the evaluation of renal function: a preliminary study.

PurposeMagnetic resonance diffusion-weighted imaging (MR-DWI) is useful to assess proton motion by the computation of an apparent diffusion coefficient (ADC). This property could be used to assess renal damage, with special regard to unilateral dysfunction. The aim of this study was to estimate the correlation between ADC and the stage of chronic renal failure (CRF) using a spin-echo echo-planar imaging (SE-EPI) sequence with the sensitivity encoding (SENSE) technique.Materials and methodsFourteen patients (nine men and five women, mean age 49 years, range 22–66 years) underwent an MR examination on a 1.5-T system. Seven patients had a history of hypertension or CRF, one had Takayasu disease and one had nephrovascular hypertension. Five subjects without known kidney disease were used as controls. The glomerular filtration rate (GFR) assessed by Cockcroft-Gault’s equation was used as a functional marker. The imaging protocol consisted of T1- and T2-weighted sequences followed by a SE-EPI acquisition with a diffusion gradient of 600 s/mm2 and SENSE factor 2 and pixel-by-pixel ADC map reconstruction. In five patients, the SE-EPI-DWI sequence was repeated after i.v. administration of 1 mg of furosemide.ResultsADC was of 2.44±0.24×10−3 mm2/s in patients with normal GFR and of 2.05±0.33×10−3 mm2/s (p<0.05) in subjects with altered GFR; a significant difference was found between stage III and IV (p<0.01), whereas no differences were found between stage I and II (p=0.27) and between stage II and III (p=0.39). A good correlation was found between GFR and ADC (r=0.79; p<0.01), with no significant change after furosemide administration (p=0.7).ConclusionsDWI is a feasible MR technique for assessing renal damage. Further studies with scintigraphic correlation are needed to confirm these results and to establish reference values for this imaging technique.RiassuntoScopoLa risonanza magnetica (RM) in diffusione (diffusion weighted, DW) permette di ottenere dati quantitativi sul movimento dei protoni liberi di acqua determinando il coefficiente di diffusione apparente (apparent diffusion coefficient, ADC). Questa capacità potrebbe essere usata per stabilire il danno parenchimale renale, in particolare nelle disfunzione unilaterali. Scopo del presente lavoro è quello di valutare la correlazione tra ADC e grado di insufficienza renale cronica utilizzando una sequenza SE Eco-planare (SS-EPI) a cui è stato applicato la tecnica di SENSitivity Encoding (SENSE).Materiali e metodiQuattordici pazienti (9 maschi e 5 femmine, età media 49 anni, range 22–66) sono stati sottoposti ad esame RM con sistema ad alto campo 1,5 T; in 5 pazienti non vi erano dati anamnestici e bioumorali di nefropatia, mentre in 7 era presente storia di ipertensione arteriosa e/o IRC ingravescente, in 1 di malattia di Takayasu e in 1 di ipertensione nefrovascolare. Il protocollo prevedeva acquisizioni T1 e T2 dipendenti, nonché una sequenza SE-EPI pesata in diffusione (b-factor 600 s/mm2) con fattore SENSE 2 e ricostruzione di mappe dell’ADC. In 5 casi la SS-EPI-DW è stata ripetuta dopo somministrazione di furosemide. Il filtrato glomerulare è stato ottenuto mediante metodo di Cockroft-Gault.RisultatiL’ADC nei soggetti normali ed i pazienti in stadio I è stato di 2,44±0,24×10−3 mm2/s, mentre quello dei pazienti in stadio II–IV è stato di 2,05±0,33×10−3 mm2/s (p<0,05). Non è stata rilevata una differenza significativa dell’ADC tra stadio I e stadio II (p=0,27) e tra stadio II e stadio III (p=0,39), mentre la differenza è stata significativa tra pazienti in stadio III e IV(p<0,01). Si è rilevata una significativa correlazione tra la clearance della creatinina (ClCr(CG)) e l’ ADC parenchimale (r=0,79; p<0,01). La furosemide non ha determinato modificazioni dell’ADC (p=0,7).ConclusioniLa RM-DW permette di ottenere valori quantitativi del coefficiente di diffusione correlabili con la funzione renale separata, senza somministrare mezzo di contrasto e con rapidi tempi d’esame. Ulteriori studi di correlazione con i dati scintigrafici e su più ampie casistiche sono necessari al fine di confermare tali risultati e stabilire valori di riferimento per questa metodica.

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

Background: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer, the anti-angiogenic, and anti-tumor activity of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF) Patients and Methods: Forty-eight patients (42 males and 6 females) with stage IIIB/IV non-small-cell-lung-cancer, a mean age of 68 years, and ECOG ≤ 2 were enrolled in the study. They received every three weeks fractioned cisplatinum (30 mg/sqm, days 1-3) and oral etoposide (50 mg, days 1-15) and were divided in 5 cohorts receiving different bevacizumab dosages [0; 2.5; 5; 7.5; and 10 mg/kg] on the day 3. Results: The combined treatment was able of inducing a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab there was an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15% respectively, with a time to progression of 7.6 months. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within three months, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. Conclusion: The combination of bevacizumab with a dose/dense chemotherapy regimen resulted moderately safe but showed significant anti-angiogenic, and anti-tumor activity.

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report

PurposeThis study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (VDWI) and compared it with conventional T2-weighted volumetry (VC) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT).Materials and methodsFourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate VC. A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm2 and volume (VDWI) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen.ResultsInterobserver agreement was 0.977 [(95% confidence interval (CI) 0.954–0.989) and 0.956 (95% CI 0.905–0.980) for VC and VDWI and 0.964 (95% CI 0.896–0.988) and 0.271 (95% CI-0.267 to 0.686) between VC and VDWI before and after CHRT. The correlation between TRG and VC and VDWI was, respectively, rho = 0.597 (p<0.05) and r2=0.156 (p=0.162) and rho=0.847 (p<0.001).ConclusionsVDWI seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.RiassuntoObiettivoScopo del nostro lavoro è stato valutare la fattibilità della volumetria in risonanza magnetica (RM) con immagini pesate in diffusione (VDWI) e confrontare tale metodo con la volumetria convenzionale (VC) basata su immagini T2-pesate in pazienti affetti da neoplasia rettale trattati con chemio-radioterapia (CHRT).Materiali e metodiQuattordici pazienti affetti da neoplasia rettale documentata istologicamente sono stati esaminati con RM prima e dopo chemio-radioterapia. Due osservatori hanno estrapolato indipendentemente il VC dalle immagini T2-pesate e il VDWI dall’acquisizione spin echo (SE)-echo-planar imaging (EPI)-diffusion-weighted (DW) (b-value 800 s/mm2) mediante segmentazione semiautomatica dell’iperintensità patologica. Le due volumetrie sono state comparate e correlate al grado di regressione tumorale sul pezzo operatorio (tumor regression grade, TRG).RisultatiL’accordo inter-osservatore per VC e VDWI è stato di 0,977 (95% intervallo di confidenza 0,954–0,989) e 0,956 (95% intervallo di confidenza 0,905–0,980) e tra VC e VDWI pre- e post-CHRT di 0,964 (95% intervallo di confidenza 0,896–0,988) e 0,271 (95% intervallo di confidenza −0,267–0,686). La correlazione tra TRG e VC e VDWI è stata rispettivamente di rho=0,597 (p<0,05) e rho=0,847 (p<0,001).ConclusioniLa VDWI sembra essere promettente per valutare la risposta alla CHRT nelle neoplasie rettali, tuttavia sono necessari ulteriori studi su casistiche più ampie al fine di migliorare la qualità di tale metodo e per valutarne il reale valore predittivo.

Magnetic resonance imaging in the evaluation of the gastric emptying and antral motion: Feasibility and reproducibility of a fast not invasive technique

PURPOSE The aim of this study was to evaluate reproducibility of a fast MRI protocol to measure gastric emptying and motility of the gastric antrum. METHODS AND MATERIALS Gastric emptying and antral speed were measured in 12 type 1 diabetic patients (mean age 43 years) and 9 healthy volunteers (mean age 31 years). Subjects, fasting from 6h, were evaluated in supine position using a 1.5T MR scanner and a eight-channels phased-array body coil after ingestion of 400 ml of a vanillas pudding mixed with 5 ml of Gd-DTPA. Axial 3D T1w sequence at 0 and 30 min for volume evaluation and cine-steady state acquisition every 5 min for a total time of 30 min for gastric wave speed assessing were acquired. Two blinded observers extrapolated T(1/2) from gastric volume assessment and speed of gastric waves. RESULTS All the patients tolerated the examination. The T(1/2) cut-off was of 115 min with an accuracy in differentiate controls from diabetics of 96% (95% CI 0.766-0.992; p<0.001), while the antral speed cut-off was of 0.15 mm/s with an accuracy of 87% (95% CI 0.628-0.977; p<0.001). The inter-observer agreement for the volumes at time 0 and 30 min was respectively 0.983 (95% CI 0.9628-0.9929; p<0.001) and 0.9933 (95% CI 0.9847-0.9971; p<0.001) with an agreement of 0.9918 (95% CI 0.9853-0.9954; p<0.001), while for antral speed it was of 0.935 (95% CI 0.9097-0.9528; p<0.001). CONCLUSIONS MRI is a reproducible technique for the evaluation of gastric emptying and antral motility.

MSCT multi-criteria: A novel approach in assessment of mediastinal lymph node metastases in non-small cell lung cancer

PURPOSE To evaluate the accuracy of multi-slice computed tomography (MSCT) in diagnosing mediastinal lymph node metastases in patients with non-small cell lung cancer (NSCLC) using a multi-criteria approach. METHODS We retrospectively reviewed contrast-enhanced MSCT of the chest in 86 consecutive patients with histopathologically proven NSCLC. All patients underwent surgical lymph node resection within 30 days from the CT examination. In all cases pathological and CT results were reviewed and correlated. RESULTS The sensitivity, specificity, positive and negative predictive values, and accuracy of MSCT using a multi-criteria approach in the detection of the N2 stage were 100%, 98.5%, 100%, 94.4% and 98.8% respectively, whereas using the size criterion alone 64%, 61%, 87%, 40%, and 62% respectively. CONCLUSIONS To improve MSCT accuracy for diagnosing N staging other criteria can be associated with lymph node size. The use of different dimensional cut-offs for each mediastinal lymph node station, the matching of positive nodal stations with tumour location, the structural characteristics and the type of enhancement allow for a high accuracy of MSCT in the staging of mediastinal nodes in NSCLC.

Three–dimensional analysis of pulmonary nodules by MSCT with Advanced Lung Analysis (ALA1) software

Purpose.The purpose of this study was to test the reproducibility of the three–dimensional (3D) Advanced Lung Analysis software (3D–ALA, GE Healthcare) in the estimation of pulmonary nodule volume.Materials and methods.We retrospectively reviewed the unenhanced multislice CT scans (Lightspeed Pro 16 GE) of 77 patients with a solitary pulmonary nodule (n=71) or metastatic pulmonary disease (n=6). A total of 103 pulmonary nodules (19 well–circumscribed, 45 juxtavascular and 39 juxtapleural) were analysed grouped into five classes based on diameter: <5 mm, 10 nodules (9.7%); ≥5 to <10 mm, 25 nodules (24.2%); ≥10 mm to <15 mm, 41 nodules (39.8%); ≥ 5 to <18 mm, 14 nodules (13.6% ); ≥ 8 to <30 mm, 13 nodules (12.62%). The following acquisition parameters were used: slice thickness 0.625 mm, reconstruction interval 0.4 mm, pitch 0.562:1, 140 kV, 300 mAs, field of view 13 cm, bone kernel. For each of the 103 nodules three, 3D volume measurements were obtained by the 3D–ALA software. The reproducibility of nodule segmentation was evaluated according to a visual score (1=optimal, ≥95%; 2=fair, 90–95%; 3=poor, ≤90%) by three observers working in consensus. The reproducibility of volume estimation was evaluated by comparing all 3D volume measurements and all segmentations obtained for each pulmonary nodule using the ANOVA test.Results.ALA–1 software allowed segmentation in all nodules (type 1 segmentation n=43, type 2 n=35, type 3 segmentation n=25). ALA–1 provided an identical 3D volume measurement in 62 nodules: [16 out of 19 well circumscribed (84.2%), 31 out of 45 juxtavascular (68.8%), 15 out of 39 juxtapleural (38.4%)]. Repeatability of 3D volume measurement was not possible in 41 out of 103 nodules [3 out of 19 (15.7%) well–circumscribed, 14 out of 45 (31.1%) juxtavascular, 24 out of 39 (61.5%) juxtapleural]. Among the 41 nodules with nonrepeatable 3D volume measurement, segmentation was scored as 1 in 2 out of 41 (4.8%), as 2 in 15 out of 41 (36.5%) and as 3 in 24 out of 41 (58.5%). The difference between the mean volume on three measurements and each type of nodule was not statistically significant (p>0.05).Conclusions.Three–dimensional volume measurement with ALARiassunto 1 software is reproducible for all nodules as regards dimension and site. ALA–1 software provided a good and reproducible volume measurement in well–circumscribed and most juxtavascular nodules. Volumetric evaluation and reproducibility of volume estimation in juxtapleural pulmonary nodules, particularly those adjacent to diaphragmatic pleura, is inadequate, and software improvement is needed.

Diffusion-weighted MR Volumetry for Assessing the Response of Rectal Cancer to Combined Radiation Therapy with Chemotherapy

Editor: In the study by Curvo-Semedo and colleagues (1), which appeared in the September 2011 issue of Radiology, the utility of tumor volumetry derived from diffusion-weighted (DW) magnetic resonance (MR) images was evaluated in the assessment of patients with rectal cancer after preoperative combined radiation therapy with chemotherapy (CRT). They showed that post-CRT DW volumetry and volume shrinkage at both T2-weighted and DW MR imaging were highly accurate in the determination of complete response (areas under the receiver operating characteristic curve [AUC] of 0.93, 0.84, and 0.92, respectively). The apparent diffusion coefficient (ADC) and ADC modification rate were not accurate (AUC, 0.54 and 0.51, respectively). The intraclass correlation coefficient (ICC) between T2-weighted and DW MR volumetry was good for pre-CRT measurements but unsatisfactory for post-CRT measurements. This last observation might be attributable to post-CRT fibrosis, which affects the reliability of segmentation of tumor volume on T2-weighted images with respect to post-CRT DW volumetry based on ADC maps (1). In their study, Curvo-Semedo and colleagues defined complete response as tumor regression grade 1 (2) at pathologic examination or a relapsefree follow-up of 17 months. The preliminary results of our study (3), performed with DW imaging using a b value of 800 sec/mm2, are consistent with those reported by Curvo-Semedo and colleagues. In our study of 21 patients who underwent surgical resection after CRT, the interobserver agreement was good (ICC = 0.948 for T2-weighted MR volumetry and 0.916 for DW MR volumetry), whereas the preand post-CRT DW and T2-weighted volumetry concordance consisted of ICC values of 0.828 and 0.151, respectively. The volume segmented from the DW data set on the basis of hyperintensity of hypercellular tissue on DW images showed a good correlation with tumor regression grade (r = 0.556, P , .05). However, DW MR volumetry has some drawbacks, including the difficulty in detecting small neoplastic residual tumors on the post-CRT ADC maps and T2 shinethrough artifacts, owing to necrosis or mucin, which can produce overestimation of residual tumor at the only qualitative eval uation of DW images. These limitations, in our experience, make it difficult to differentiate between patients with tumor regression grades of 1 or 2 (Mandard five-point scale). The relationship to DW MR volumetry of the nodal stage evaluation could increase its prognostic relevance because good prognosis has been demonstrated for low tumor regression grades ypN2 with respect to ypN+ (4). DW MR volumetry seems to be a promising tool for assessing response after preoperative CRT and deserves further study.

Water/cortical bone decomposition: A new approach in dual energy CT imaging for bone marrow oedema detection. A feasibility study

INTRODUCTION Many studies aimed at validating the application of Dual Energy Computed Tomography (DECT) in clinical practice where conventional CT is not exhaustive. An example is given by bone marrow oedema detection, in which DECT based on water/calcium (W/Ca) decomposition was applied. In this paper a new DECT approach, based on water/cortical bone (W/CB) decomposition, was investigated. MATERIALS AND METHODS Eight patients suffering from marrow oedema were scanned with MRI and DECT. Two-materials density decomposition was performed in ROIs corresponding to normal bone marrow and oedema. These regions were drawn on DECT images using MRI informations. Both W/Ca and W/CB were considered as material basis. Scatter plots of W/Ca and W/CB concentrations were made for each ROI in order to evaluate if oedema could be distinguished from normal bone marrow. Thresholds were defined on the scatter plots in order to produce DECT images where oedema regions were highlighted through color maps. The agreement between these images and MR was scored by two expert radiologists. RESULTS For all the patients, the best scores were obtained using W/CB density decomposition. CONCLUSIONS In all cases, DECT color map images based on W/CB decomposition showed better agreement with MR in bone marrow oedema identification with respect to W/Ca decomposition. This result encourages further studies in order to evaluate if DECT based on W/CB decomposition could be an alternative technique to MR, which would be important when short scanning duration is relevant, as in the case of aged or traumatic patients.

Diffusion-Weighted Magnetic Resonance Diagnosis of Local Recurrences of Prostate Cancer after Radical Prostatectomy: Preliminary Evaluation on Twenty-Seven Cases

Objectives. To assess the diagnostic performance of diffusion-weighted MR imaging (DWI) in patients affected by prostatic fossa (PF) relapse after radical prostatectomy (RP) for prostatic carcinoma (PC). Methods. Twenty-seven patients showing a nodular lesion in the PF at T2-weighted MR imaging after RP, with diagnosis of PC relapse established by biopsy or PSA determinations, were investigated by DWI. Two readers evaluated the DWI results in consensus and the apparent diffusion coefficient (ADC) of the nodules, separately; a mean value was obtained (ADCm). Results. Relapses did not significantly differ in size in respect of postsurgical benign nodules. The DWI qualitative evaluation showed sensitivity, specificity, accuracy, ppv, and npv values, respectively, of 83.3%, 88.9%, 85.2%, 93.7%, and 72.7% (100%, 87.5%, 95.6%, 93.7%, and 100%, for nodules >6 mm). The intraclass correlation coefficient (ICC) for ADC evaluation between the two readers was 0.852 (95% CI 0.661–0.935; P = 0.0001). The ADCm values for relapses and benign nodules were, respectively, 0.98 ± 0.21 × 10−3 mm2/sec and 1.24 ± 0.32 × 10−3 mm2/sec (P = 0.006). Sensitivity, specificity, accuracy, ppv and npv of ADCm were, respectively, 77.8%, 88.9%, 81.8%, 93.3%, and 66.7% (93.3%, 87.5%, 85.4%, 93.3%, and 87.5% for nodules >6 mm). Conclusions. Diffusion-weighted MR imaging is a promising tool in the management of a hyperintense nodule detected by T2-weighted sequences. This might have a relevant importance in contouring radiotherapy treatment volumes.

Evaluation of Motility Changes after Laparoscopic Sleeve Gastrectomy Using Magnetic Resonance Imaging

We have read with interest the recent work on gastric motility evaluation in laparoscopic sleeve gastrectomy (LSG) by using magnetic resonance imaging (MRI) [1]. The authors performed MR examination in five female patients before and after LSG, using a wide-bore MR scanner (70 cm), and, after, drinking 500 ml of tiepid water. Two fast sequences were used to evaluate gastric volume and morphometry and speed of the antral folds. They found an acceleration of the gastric emptying after surgery, explaining that on the basis of both gastric pacemaker removal and interstitial cells of Cajal network that allow the persistence of antrum motility compared to immobile “sleeve compartment”. We agree with the authors about the increasing of antral peristaltic velocity in these patients with significant reduction of gastric emptying T1/2. We have evaluated nine patients using a MR technique previously described [2], with time delay from surgery of 4–10 months, using 120 ml of vanilla pudding as gastric load (not published data), with quantitative data obtained in consensus by two observers. We have found a gastric emptying half-time of 24.02±8.16 min with a speed of antral peristalsis of 1.72±0.38 s; while in a control group of 11 subjects (population characteristics in [2]), these parameters were respectively of 101.78±41.69 min and 1.37 ±0.25 s (p=0.0004 and p=0.0042, respectively). We add that in our experience, we evaluated the gastric motility for 30 min, observing a physiological increase of antral motility in control group, as previously referred, while this change is not present in LSG patients (p=0.372, Fig. 1). So, we would like to emphasize the neurohumoral mechanisms that could affect this modifications in LSG, as correctly suggested by the authors, but also the kind and the amount of gastric load could have some influences on quantitative data sampling. This can explain the lower antral speed detected in our controls compared to that referred by the authors in the presurgical assessment [1, 2]. In this regard, we would like to warn the authors about the use of water that could produce a drawback in quantitative assessment due to influence of posture and gravity for liquids in gastric emptying [3, 4]; furthermore, steady-state imaging with a semisolid homogeneous food (like pudding) could be more achievable for gastric function evaluation, because of the marked contrast between stomach and neighboring structures produced by this kind of food [5]. Another limitation, in our opinion, concerns the need to evaluate the reproducibility of data extrapolation from imaging over all for antral speed assessment. In fact, the measurement of peristaltic wave speed is feasible with a good confidence in unresected stomach, as we assessed previously [2], but it could be difficult when gastric anatomy is modified by surgery. We found a not significant interobserver agreement for our data (k=0.042) about antral speed parameter, while the agreement was significant for gastric emptying evaluation (k>0.75). Finally, it is very important to emphasize the use in this study of a wide-bore MR scanner. This system was useful to the authors for the examination of patient with BMI>40 before surgery that is unfeasible with a regular bore scanner, as we experienced in our clinical practice. Obviously, the cost of this technique at present makes it S. F. Carbone (*) :A. Bancheri : L. Volterrani Department of Radiology, University Hospital of Siena, Viale Bracci, 53100 Siena, Italy e-mail: fracarb@gmail.com