Aldo Morra

We applied the new technique of virtual endoscopy to the middle ear because this anatomical area is characterized by favorable contrast. CT examinations of the petrous bone were obtained using 1.5 mm thick 1 coronal axis slices, with 1 mm or 1.5 mm table feed, 120 kV, 140-170 mA and 2 s scan time. The images were reconstructed with the high resolution algorithm for bony structures and a small field of view (9.6 cm), separately for the right and left petrous bone. The images were then transferred on a workstation and processed with the Navigator virtual endoscopic software (General Electric). A threshold value ranging -350 to -600 HU was applied. A series of images is acquired as the virtual endoscope moves from the external auditory canal to the middle ear cavity. Images of the anterior, medial, and posterior surfaces of the middle ear are presented. Different views of the ossicles are also presented. High quality images were always obtained for the middle ear structures, including the ossicles. CT endoscopy of the middle ear provides a new view of the anatomy of this complex area. It has some advantages and disadvantages; the former can be summarized as follows: -demonstration of areas which are difficult to show with endoscopy because of the presence of membrana tympani; -the virtual endoscope can be placed in several positions and therefore it can be inserted in all sites and tortuous places of anatomical cavity; -nice and effective demonstration of the ossicular chain including the stapes. The disadvantages are related to the fact that the endoscopic reconstruction (such as any other three-dimensional reconstruction) is a representation of surfaces where different densities are necessarily homogenized. CT virtual endoscopy of the middle ear can currently be considered a complementary technique to conventional CT because it permits better anatomical detailing of this complex region.

Virtual endoscopy is a new 3D technique which permits to depict the inner surface of anatomic cavities. We report our experience in the study of the nasal cavity and paranasal sinuses. CT examinations of the maxillofacial region were obtained using 1.5 or 3.0 mm slices, 1.5 or 3.0 mm table feed, 120 kV, 140 mA, 2 s scan time, standard and high resolution algorithms for bony structures and a field of view of 14-16 cm. The images were transferred on a workstation and processed with the Navigator virtual endoscopy software (General Electric). A threshold value ranging -300 to -550 UH was applied. We report a series of virtual images of the nasal cavity which includes rhinopharynx vault, torius tubarius, choanae, turbinates, tubal orifice and osteomeatal complex. Moreover, images of frontal sinus and tear duct, of polyps and fracture of maxillary sinus are also presented. 3D virtual endoscopy provides a clear visualization of the anatomic structures of the nasal cavity and sinuses. The images are similar to those of conventional endoscopy. Moreover virtual endoscopy visualizes the paranasal sinuses, which are not accessible at conventional endoscopy. The main limitations of this new technique are the arbitrary choice of the threshold value and the homogenization of different tissue densities, which reduces the contrast resolution. Virtual endoscopy can presently be considered a complementary technique of the standard axial and coronal CT examination. It provides an effective demonstration of the anatomy of these structures and shows areas which are difficult to visualize with conventional endoscopy. This technique could be of help in didactical activity; its clinical application has to be verified.

Virtual CT colonoscopy is a novel technique whose diagnostic accuracy and clinical yield are currently investigated. Several studies have shown its capabilities in detecting colon and rectal cancers. We report the results of a preliminary experience with the volume rendering technique and compare CT colonoscopy with endoscopy and surgery. Our series consisted of 25 patients with colon cancer confirmed at endoscopy and/or surgery. All examinations were carried out with a spiral CT scanner Philips Tomoscan AVE1. Intestinal preparation was adequate in all patients, consisting in gas insufflated immediately before acquisition, after the injection of 100 mL iodinated contrast agent. All examination were performed in prone position using axial 5 mm slices with 5 mm table feed (pitch 1) and 2 mm reconstruction index; 120 kV and 200-250 mA were used. Images were transferred to a workstation (Easy Vision, Philips, release 4.2.1.1) for processing. We acquired multiplanar (MPR) and virtual endoscopic images with volume rendering; the selected threshold was -250 to -600 Hounsfield Units. Virtual endoscopic images could be obtained in 23 of 25 cases. The results of the radiological study were compared with endoscopic and surgical findings in 25 and 17 cases, respectively. Endoscopy and surgery detected 46 lesions: 29 were malignant and 17 benign. Axial CT and MPR alone detected 35 lesions (76%), 29 of them malignant and 6 benign. The 11 benign lesions missed by axial CT ranged 6-8 mm in diameter. There were no false positives. CT colonoscopy alone detected 66 lesions, but 22 of them were false positive due to residual stool in the colon (21 cases) and to residual barium in the colon (1 case). Combining CT colonoscopy and axial and MPR images enabled to correct the false positive diagnoses made by CT colonoscopy alone and to decrease the false negative ratio of axial and MPR images. Forty-one of 44 lesions (93%) were detected. Thirty-seven lesions were found in the 17 surgical patients; 34 of them were correctly identified combining CT colonoscopy and axial and MPR findings, while endoscopy detected only 31 lesions. Thus, CT had 92% sensitivity, versus 83% of fiberoptic endoscopy. In this preliminary experience volume rendering CT colonoscopy exhibited high sensitivity in detecting colon cancers, but their correct evaluation and characterization can be obtained if axial and MPR studies are combined. Further investigation and technological developments are necessary to define the yield of this new technique.

In this paper we present an overview of CT-Urography. With the advent of multislice CT scanners and the evolution of image processing methods this technique now affords optimal urographic images comparable to those obtained with conventional techniques. We describe the acquisition techniques and protocols used by the various authors. Effective radiation dose has conditioned the use of CT-Urography so that the tendency today is to reduce the number of scans by performing, after the nonenhanced scan, a single contrast-enhanced scan comprising both the nephrographic and urographic phase. With the use of multislice CT the quality of the urogram improves with the number of slices. We illustrate a variety of processing techniques, multiplanar reconstruction (MPR), maximum (MIP) and average intensity projection (AIP) and volume rendering (VR) and present a series of upper urinary tract tumours testifying to the superiority of the AIP technique over MIP. We then review the results of compar...

To evaluate a new virtual endoscopy software package capable of automatically plotting the path along which to perform endoscopic exploration. We reviewed the examinations of 50 patients with colonic neoplasms studied by CT colonoscopy by using a single-detector CT scanner (Philips Tomoscan AVE1). The technical parameters used were: slice thickness 3 mm, pitch 1.4, reconstruction interval 2-2.5, 120 kV, 150-200 mA. The images were processed on a separate workstation (Philips Easy Vision 5.1) running an experimental virtual endoscopy software package capable of automatically drawing a line along which to move the virtual endoscope to explore the colon. Reconstruction of the endoscopic images along the path obtained was set at an interval of 15-20 mm between one endoscopic view and the next, to a total of 70 to 120 images. The endoscopic animated image sequence was then saved and evaluated by comparing the starting axial images and the three-dimensional images obtained. The programme plotted the endoscopic path correctly in a single pass in 40 of the 50 cases studied. The overall time spent by the radiologist on image-processing did not exceed 5 minutes. The need to reduce the time spent by audiologists on post-processing has led to a gradual improvement in image-processing hardware and software. In the context of virtual endoscopy, one of the main goals is to obtain the path for endoscopic exploration in as short a time as possible. The programme we evaluated successfully fulfils this requirement as, once the image-processing technical parameters have been defined, it plots a path along the entire colon and performs the reconstruction procedures automatically. The time spent by the operator on post-processing does not exceed 5 minutes. The new programme evaluated in this study facilitates the processing of endoscopic images, reduces radiologist time and may contribute to the widespread use of virtual colonoscopy.

Urothelial tumors of the upper urinary tract (renal pelvis and ureters) are rare: the most common of these are Transitional Cell Carcinomas (TCC), usually localized in the bladder (75% of cases), whereas only 7-10% arise in the renal pelvis and 2,5-5% in the ureter. Multicentricity is not infrequent and synchronous or metachronous tumors have been reported to develop in 11-13% of patients with upper urinary tract cancer and 2-4% of those with bladder cancer. The presence of additional lesions can change patient management. Clinically these tumors may present with hematuria or flank pain, but sometimes there are no specific clinical findings. Radiological studies play an important role in tumor detection and staging and in follow up. The diagnosis is usually performed by IVU and US, while CT is generally employed in the staging. Our purpose was to verify the role of Spiral CT with Multiplanar Reconstructions (MPRs) in the evaluation of ureteral tumors. Nine patients with ureteral neo...

Patients with combined valvular-aortic disease undergo surgical reconstruction of the aortic root with a valved composite graft. Two of the techniques used to replace the aortic valve and ascending aorta are Bentall and Cabrol procedures. Cabrol surgical procedure uses a Dacron tube that enables coronary artery revascularization. Graft limb occlusion may however occur. Digital subtraction angiography, magnetic resonance angiography and multidetector computed tomography angiography are useful imaging methods for the evaluation of surgical-related complications. We report the case of a patient treated by the Cabrol technique, who was studied with contrast-enhanced multidetector computed tomography angiography to evaluate long-term post-surgical complications and coronary vessels patency.

This report presents a case of a 16-year-old hypertensive boy who presented to our clinic. Laboratory findings showed severe hypokalemia and markedly increased plasma renin activity. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion (2 cm) in the lower pole of the left kidney. The patient underwent nephron-sparing surgery. Histopathologic examination gave a diagnosis of juxtaglomerular cell tumor. Reninoma is an uncommon cause of hypertension in a young adult and should be included in the differential diagnosis as a potential life-threatening and curable condition. The conservative surgical management is the gold standard for small, circumscribed lesions.

Congenital anomalies of the coronary arteries, even if rare, may have sudden death or myocardial infarction as the first clinical manifestations: thus, it is clear that an early diagnosis has a paramount importance for patients at risk. We present a set of cases advocating the use of multi-slice computed tomography (MSCT) in the detection of coronary artery anomalies. The majority of cases had previously undergone conventional coronary angiography, which, despite being considered the gold standard for the diagnosis of the coronary artery pathologies, often yielded incomplete results. In 439 consecutive patients examined over 22 months by MSCT for the study of heart and coronary arteries, 11 were diagnosed for anomalous coronary artery. All patients were symptomatic for one or more of the following: chest pain, dyspnoea, palpitations, myocardial infarction and resuscitated cardiac arrest. Eight patients had previously undergone a coronary angiography. In the selected patients, seven different types of coronary anomalies were found by MSCT examination. In all cases, this technique was able to recognize the origin of the anomalous coronary artery, its three-dimensional course and its spatial relationship with the adjacent structures, even when conventional coronary angiography was performed but was unable to provide sufficient information for a correct and complete diagnosis. MSCT is an accurate technique for detecting coronary artery anomalies and visualizing their three-dimensional origin and course, and their relationship with the great vessels. It may be considered as the first-choice imaging modality when an anomalous coronary artery is suspected.

In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27 with Chronic Hepatitis C (CHC) F1-F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.37 m/s) in comparison with controls (2.19 m/s, P<0.001), CHC patients (2.37 m/s, P<0.001), and cirrhotic patients without EV (2.7 m/s, P<0.001). Moreover, VTTQ-SS was significantly higher among cirrhotic patients without EV in comparison with both controls (P<0.001) and CHC patients (P<0.01). The optimal VTTQ-SS cut-off value for predicting EV was 3.1 m/s (AUROC=0.96, sensitivity 96.4%, specificity 88.5%, positive predictive value 90%, negative predictive value 96%, positive likelihood ratio 8.36, and negative likelihood ratio 0.04). In conclusion, VTTQ-SS is a promising noninvasive and reliable diagnostic tool to screen cirrhotic patients for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut-off value of 3.1 m/s, we would avoid endoscopy in around 45% of cirrhotic subjects, with significant time and cost savings.

The cardiac electric impedance was recorded between right atrium and ventricle, throughout the cardiac cycle, by means of a tripolar single pass lead for VDD pacing. The transvalvular impedance signal (TVI) is a sharp periodic wave, with high signal-to-noise ratio, that is detected exclusively in the presence of cardiac mechanical activity. The minimum TVI value is attained during the atrial systole, the maximum at the end of ventricular systole. Different parameters of TVI waveform are affected by changes in the inotropic state, and could therefore be proposed as potential signals for new rate responsive algorithms based on the correlation between inotropic and chronotropic regulation. The signal might be used, moreover, for pacing and sensing validation in autoregulating pacemakers and for fibrillation recognition in ICDs.

Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) have therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal antibody, tremelimumab, in advanced malignant mesothelioma. In our open-label, single-arm, phase 2 study, we enrolled patients aged 18 years or older with measurable, unresectable malignant mesothelioma and progressive disease after a first-line platinum-based regimen. Eligible patients had to have a life expectancy of 3 months or more, an Eastern Cooperative Oncology Group performance status of 2 or less, and no history of autoimmune disease. Patients received tremelimumab 15 mg/kg intravenously once every 90 days until progressive disease or severe toxicity. The primary endpoint was the proportion of patients who achieved an objective response (complete or partial response), with a target response rate of 17% according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural malignant mesothelioma or standard RECIST 1.0 for peritoneal malignant mesothelioma. Analyses were done according to intention to treat. This trial is registered with EudraCT, number 2008-005171-95, and ClinicalTrials.gov, number NCT01649024. Between May 27, 2009, and Jan 10, 2012, we enrolled 29 patients. All patients received at least one dose of tremelimumab (median two doses, range one to nine). No patients had a complete response and two patients (7%) had a durable partial response (one lasting 6 months and one lasting 18 months); one partial response occurred after initial progressive disease. Thus, the study did not reach its primary endpoint. However, we noted disease control in nine (31%) patients and a median progression-free survival of 6·2 months (95% CI 1·3-11·1) and a median overall survival of 10·7 months (0·0-21·9). 27 patients (93%) had at least one grade 1-2 treatment-emergent adverse event (mainly cutaneous rash, pruritus, colitis, or diarrhoea), and four patients (14%) had at least one grade 3-4 treatment-emergent adverse event (two gastrointestinal, one neurological, two hepatic, and one pancreatic). Although the effect size was small in our phase 2 trial, tremelimumab seemed to have encouraging clinical activity and an acceptable safety and tolerability profile in previously treated patients with advanced malignant mesothelioma. Associazione Italiana per la Ricerca sul Cancro, Istituto Toscano Tumori, Pfizer, and Fondazione Buzzi Unicem.

Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated. 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed. We found a significant global cortical thinning in p-MS (2.22 +/- 0.09 mm), RR-MS (2.16 +/- 0.10 mm) and SP-MS (1.98 +/- 0.11 mm) compared to CIS (2.51 +/- 0.11 mm) and HV (2.48 +/- 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = -0.393, p = 0.03) and absent in p-MS (r = -0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas. Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.

Epilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR. We applied the double inversion recovery (DIR) sequence in relapsing remitting MS (RRMS) patients with or without epileptic seizures in order to clarify the relationship between ICLs and epilepsy in MS in vivo. Twenty RRMS patients who had epileptic seizures (RRMS/E) during the course of the disease were studied for the presence of ICLs. A group of 80 RRMS patients with no history of seizures and matched for gender, age, disease duration, Expanded Disability Status Scale (EDSS) grading, and T2 lesion volume (T2-WMLV) was selected as reference population. ICLs were detected by applying the DIR sequence. ICLs were observed in 18/20 (90%) RRMS/E and in 39/80 (48%) RRMS (p = 0.001). RRMS/E showed five times more ICLs (7.2 +/- 8.4) than RRMS (1.5 +/- 2.4; p = 0.015). The total ICLs volume was 6 times larger in RRMS/E than in RRMS (1.2 +/- 1.7 cm3 versus 0.2 +/- 0.2 cm3, p = 0.016). No significant difference was observed between RRMS and RRMS/E with regard to the number and volume of juxtacortical lesions and T2-WMLV. Our findings indicate that RRMS/E have more extensive cortical inflammation than RRMS patients with no history of epilepsy. Inflammatory ICLs may be responsible for epilepsy in MS.

Angiosarcomas are rare soft tissue malignancies. Typically they originate from the skin of the scalp or face, whereas visceral sarcomas are very rare. We report the case of a 67-year-old man affected by a large angiosarcoma of the kidney. After surgical removal, a rapid peritoneal, visceral and cutaneous diffusion developed. Palliative chemotherapy, based on anthracycline and ifosfamide, which are normally used to treat all other high-grade spindle cell sarcomas, was totally inactive. On the basis of these results and of the biological characteristics of these rare neoplasms it is mandatory to develop other therapeutic approaches. Antiangiogenetic agents are of interest for this disease due to the peculiar origin of the cells of these sarcomas.

Recent fMRI evidence indicates that both the execution and the observation of hand actions in multiple sclerosis (MS) patients increase recruitment of a portion of the so-called mirror neuron system. However, it remains unclear whether this is the expression of a compensatory mechanism for the coding of observed action or whether such a mechanism represents a rather unspecific functional adaptation process. Here we used fMRI on early relapsing remitting MS (RRMS) patients to clarify this issue. Functional images of 15 right-handed early RRMS patients and of 15 sex- and age-matched right-handed healthy controls were acquired using a 1.5 T scanner. During scanning, participants simply observed images depicting a human hand either grasping an object or resting alongside an object. As shown by a between-group analysis, when compared to controls, RRMS patients revealed a robust increase of activation in an extensive network of brain regions including frontal, parietal, temporal and visual areas usually activated during action observation. However, this pattern of hemodynamic activity was completely independent of the type of observed hand-object interaction as revealed by the lack of any significant between-group interaction. Our findings are in line with previous fMRI evidence demonstrating cortical reorganization in MS patients during action observation. However, based on our findings we go one step further and suggest that such functional cortical changes may be the expression of a generalized and unspecific compensatory mechanism, that is not necessarily involved in action understanding.

A significant inflammatory pathologic disorder in the cortex of patients with multiple sclerosis (MS) has been demonstrated by ex vivo studies. To determine the frequency, time of appearance, and clinical relevance of intracortical lesions (ICLs) in MS in vivo. Double inversion recovery sequence study. Multiple Sclerosis Centre of the Veneto Region. Patients We enrolled 380 patients (116 with clinically isolated syndrome [CIS], 163 with relapsing-remitting MS [RRMS], and 101 with secondary progressive MS [SPMS]) and 40 age- and sex-matched healthy volunteers between May 1, 2005, and December 31, 2006. We assessed the frequency and number of ICLs and brain parenchyma fraction, white matter T2 lesion volume, and clinical disability. Although never observed in healthy volunteers, ICLs were detected in 58% of patients (36% of patients with CIS, 64% of patients with RRMS, and 73% of patients with SPMS). The number of ICLs was higher in patients with SPMS than in those with CIS or RRMS (P <.001), and patients with ICLs had a higher Expanded Disability Status Scale score (P = .004), a higher white matter T2 lesion volume (P = .008), a lower brain parenchyma fraction (P = .009), and a higher frequency of IgG oligoclonal bands (IgGOBs) (P <.001) than patients without ICLs. Patients positive for IgGOBs had more ICLs than patients negative for IgGOBs (P = .02). The number of ICLs correlated with the Expanded Disability Status Scale score (r = 0.48, P <.001), white matter T2 lesion volume (r = 0.38, P = .001), and brain parenchyma fraction (r = -0.47, P = .001). A significant association between ICLs and male sex was observed. Although more frequent in patients with SPMS, ICLs were observed from the early disease stages. The ICLs were more frequently detected in patients with IgGOBs and were associated with a higher clinical disability score and male sex. The ICLs may help to define MS clinical heterogeneity and prognosis in clinical settings.

This work uses a new programme for producing 3D radiological images acquired by means of CT which enables the internal surfaces of the examined structures to be visualized. This new method, which is able to navigate inside organs in a similar way to fibreoptic endoscopy, is known as virtual endoscopy. CT examinations of the temporal bone were carried out using spiral equipment and endoscopic 3D processing was carried out on a separate workstation equipped with a volume-rendering programme. Once the technical parameters necessary for obtaining a representation of the internal surfaces had been defined, a simulation of a virtual otoscopy was conducted by moving the virtual endoscope from the external auditory canal through the annulus to the tympanic cavity. The simulation can be obtained either by moving the endoscope by hand, using the mouse, or by defining a path along which the software automatically creates an endoscopic 3D reconstruction. The images thus obtained are projected sequentially to give a "movie" effect, i.e. a continuous progression of the endoscope. The average time required to conduct the procedure ranges from 20 to 30 min. A virtual endoscopic visualization of the middle ear was obtained which, in particular, generated images of the tympanic cavity with the ossicular chain. In our experience, virtual otoscopy shows the anatomy of the structures of the tympanic cavity in excellent detail and may be considered complementary to CT, providing useful images enabling better visual representation and understanding of this complex structure. Although clinical applications of the technique remain to be defined it may have a role to play in presurgical diagnostic evaluation of the ossicular chain, epitympanum and retrotympanum.