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Analysis of tumour samples by a proteomic technology, which combines two-dimensional gel electrophoresis and mass spectrometry analysis, is a promising approach for molecular characterization of cancer. Proteomic analysis of neoplasms is usually performed on surgical material. The possibility to perform proteomic analysis on pre-operative samples might be useful for diagnostic purposes or for determination of tumour sensitivity to therapy. In this study, we report how tissues from core biopsy of breast lesions can be routinely used to obtain accurate protein expression profiles by proteomic analysis. Protein profiles from fibroadenomas were compared to those from ductal infiltrating carcinomas. By using mass spectrometry, identification of proteins overexpressed in carcinomas with respect to fibroadenomas was obtained. Thus, our study provides a methodology to perform proteomic analysis on pre-operative samples of breast lesions.

Background: Preoperative staging of pelvic endometriosis helps the gynecologist plan therapy and offers a prognosis to patients. We compared a staging system of pelvic endometriosis based on magnetic resonance imaging (MRI) findings with the American Fertility Society (AFS) laparoscopic classification. Methods: Forty-four consecutive females with clinically suspected endometriosis underwent MRI examination to demonstrate the presence of endometriomas and pelvic implants. Laparoscopy was performed within 2 weeks. An MRI score was developed to classify endometriosis into four classes comparable to those of AFS laparoscopic staging. Concordance between MRI and laparoscopic classification was evaluated with κ statistics. Results: Laparoscopy confirmed 60 of 61 endometriomas detected by MRI. Implants were discovered in 20 of 44 patients with MRI and in 23 of 44 with laparoscopy. MRI detected 50 endometrial implants of 65 detected by laparoscopy (76.9%). With regard to endometriosis staging, we obtained a concordance between MRI and AFS classification in 42 of 44 patients (κ = 0.913). Conclusion: Although MRI has limitations such as suboptimal depiction of small implants and adhesions, this technique is very useful to guide laparoscopy. Moreover, the optimal concordance (95%) between our proposed MRI staging and the AFS laparoscopic classification demonstrated a new advantage of MRI in preoperative staging of endometriosis.

Background: It is well recognized that distinguishing benign from malignant papillary lesions of the breast may pose challenging diagnostic problems. To prospectively evaluate the potential role of mammography, ultrasound and image-guided core biopsy in the diagnosis of papillary lesions of the breast. Methods: 1,442 women consecutively underwent 14-gauge core biopsy and in 51 cases (3.5%) a diagnosis of papillary lesion was formulated. Both radiologists and pathologists independently expressed their degree of suspicion of malignancy (not suspicious, low, moderate, high) on the basis of radiological and core biopsy findings, respectively. Surgical excision of the lesion was used as gold standard and diagnostic agreement was assessed by the kappa statistic. Results: At surgery, 19 of the 49 (38.7%) resected cases had a diagnosis of malignancy. A poor agreement was found between mammography and core biopsy results in the categorization of suspicion of malignancy (k = 0.03). Similar data were obtained between ultrasound and core biopsy (k = 0.07). A poor agreement was also observed between radiological and surgical results (k < 0.20). In contrast, a good agreement was found between core biopsy and surgical samples (k > 0.70). However, 5 (26%) out of the 19 malignant cases at surgery were judged as benign or probably benign on core biopsy. Depending on how the categories of suspicion on core biopsy were set up, the range of sensitivity was 74–89%, whereas specificity ranged from 91 to 97%. Conclusions: Image-guided large core biopsy allows for a correct diagnosis in the majority of papillary lesions. However, its sensitivity is not good enough for surgical excision to be avoided.

The aim of this study was to compare the sensitivity of pulse inversion harmonic digital sonography, unenhanced transabdominal sonography, and ferumoxides-enhanced MR imaging in the depiction of liver metastases. In addition, pulse inversion harmonic digital sonography was performed at different scanning times after Levovist injection to define the best phase for depiction.Twenty-six consecutive patients with findings of extrahepatic primary malignancies and liver metastases suspected on transabdominal sonography were examined with both pulse inversion harmonic imaging and ferumoxides-enhanced MR imaging within a 7-day period. Pulse inversion harmonic imaging was performed before and at 20, 100, and 180 sec after a bolus injection of Levovist. MR imaging was performed before and after ferumoxides administration, using breath-hold gradient-recalled echo T1-weighted and turbo spin-echo short tau inversion recovery T2-weighted sequences. Two radiologists independently evaluated image quality, and the number, location, and diameter of lesions scanned using both techniques. Intraoperative sonography or at least 8-month follow-up confirmed the lesions depicted. Analyses included Wilcoxon's signed rank test and Interclass correlation test.Levovist-enhanced pulse inversion harmonic imaging revealed 104 metastases on the first scan after contrast injection, 126 on the second scan, and 118 on the third, compared with 66 on the unenhanced scan. Pulse inversion harmonic digital sonography depicted 90% of lesions shown on ferumoxides-enhanced MR imaging (140 metastases) (p = 0.001).Levovist-enhanced pulse inversion harmonic digital sonography is a sensitive technique for depiction of liver metastases. Pulse inversion harmonic digital sonography may have a potential role in imaging patients with possible metastatic involvement of the liver. Further studies are needed to define its place in the workup of these patients. At present, ferumoxides-enhanced MR imaging, being more sensitive, must be performed in all patients in whom pulse inversion harmonic digital sonography is not conclusive or when after pulse inversion harmonic digital sonography, patients remain eligible for surgery.

To compare gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging with ferumoxides-enhanced MR imaging for detection of liver metastases.Twenty consecutive patients known to have malignancy and suspected of having focal liver lesions at ultrasonography (US) underwent 1.0-T MR imaging with gradient-recalled-echo T1-weighted breath-hold sequences before, immediately after, and 60 minutes after Gd-BOPTA injection. Subsequently, MR imaging was performed with turbo spin-echo short inversion time inversion-recovery T2-weighted sequences before and 60 minutes after ferumoxides administration. All patients subsequently underwent intraoperative US within 15 days, and histopathologic analysis of their resected lesion-containing specimens was performed. Separate qualitative analyses were performed to assess lesion detection with each contrast agent. Quantitative analyses were performed by measuring signal-to-noise and contrast-to-noise ratios (CNRs) on pre- and postcontrast Gd-BOPTA and ferumoxides MR images. Statistical analyses were performed with Wilcoxon signed rank and Monte Carlo tests.Sensitivity of ferumoxides-enhanced MR imaging was superior to that of Gd-BOPTA-enhanced MR imaging for liver metastasis detection (P.05). Ferumoxides MR images depicted 36 (97%) of 37 metastases detected at intraoperative US, whereas Gd-BOPTA MR images depicted 30 (81%) metastases during delayed phase and 20 (54%) during dynamic phase. All six metastases identified only at ferumoxides-enhanced MR imaging were 5-10 mm in diameter. There was a significant increase in CNR between the lesion and liver before and after ferumoxides administration (from 3.8 to 6.8, P.001) but not before or after Gd-BOPTA injection (from -4.8 to -5.5, P.05).Ferumoxides-enhanced MR imaging seems to be superior to Gd-BOPTA-enhanced MR imaging for liver metastasis detection.

Angiosarcoma (AS) of the breast is a rare and highly aggressive vascular cancer. It presents as a primitive or radioinduced form. The case of a 46-year-old woman who underwent quadrantectomy of the breast plus axillary lymphonode dissection and radiotherapy postoperatively (QUART) for ductal infiltrant carcinoma is reported in the following. Ten years later, the patient underwent mastectomy with immediate reconstruction, for local recurrence that was diagnosed as an AS of the breast at final pathological examination. She did not receive any adjuvant treatment due to local post-operative complications related to breast reconstruction. We criticise our thrapeutic approach and we recommend more attention about local recurrence suggesting that tru-cut needle biopsy of local recurrence of the breast after QUART, should be the correct diagnostic approach.

OBJECTIVE: Inhibins and activins are members of the transforming growth factor beta superfamily and are known to modulate the growth and differentiation of several cell types. The present study investigated the localization of inhibin and activin subunits in human normal and pathological breast tissues. DESIGN: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, betaA and betaB in surgical specimens from women undergoing reductive mammoplasty (classified, according to the phase of the menstrual cycle, as follicular, luteal, or postmenopausal), and patients submitted to lumpectomy for fibrocystic disease, benign (intraductal papilloma, adenomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). METHODS: Immunohistochemistry was used to localize inhibin alpha and activin betaA and betaB subunits in the cytoplasm of epithelial cells of mammary glands. Dimeric activin A, inhibin A and inhibin B were measured by specific two-site enzyme immunoassay in the cystic fluid collected from patients with fibrocystic disease. RESULTS: An intense staining for the alpha inhibin subunit and a mild staining for betaA and betaB subunits were present in samples obtained from normal breast tissue regardless of menstrual cycle phase, and in fibrocystic disease and benign neoplasms. Carcinoma cells stained weakly to moderately for alpha subunit and were negative for betaA and betaB subunits. Fibrocystic disease was associated with absence of betaA subunit expression in normal epithelial cells and intense staining for all subunits in the apocrine cells. Immunoreactive inhibin A, inhibin B, and activin A were also present in cystic fluid, suggesting a local secretion of these proteins. CONCLUSION: These data suggest a local expression and secretion of inhibin and activin in human normal, fibrocystic disease and neoplastic breast tissues. The low expression of these proteins may facilitate abnormal cell proliferation in breast carcinoma.

The aims of this study are to determine visualization of normal phonation structures with the use of MR fast sequences and anatomical reference indices which can be used in evaluating upper resonator pathologies. A total of 12 normal subjects were studied, a 1 T system, a volumetric receiving head and neck coil and FLASH sequences for one sagittal and two coronal scans. Each subject was instructed to take a deep breath and then to produce the vowel sounds for the entire duration of the scan. The movement of the following anatomical structures were considered: lips, tongue, soft palate, pharynx and epiglottis. For each subject sagittal scans were used to measure the minimal palate tongue distance (p-t), the minimal anterio-posterior diameter of the mesopharynx (mp), and the epiglottis excursion angle (ep) with respect to the plane determined by the false vocal cords. Our results were compared with a diagrammed representation of tongue movements (vocal trapezium). This study underlines the validity of MR imaging techniques in the study of the phono-articulatory tract, because MR provided good detail of the phono-articulatory structures enabling an overall functional evaluation. MR would appear useful in evaluating defects in the velum and palate, in staging of oropharyngeal neoplasms and in surgical reconstructions of the tongue.

Both color Doppler sonography and and magnetic resonance are imaging techniques which do not use ionizing radiations, but despite this common feature there remain many differences between them. Thus, color Doppler sonography is a cost-effective technique using mechanical waves and providing real-time images while magnetic resonance imaging is much more expensive, uses magnetic fields and radiofrequency energy and provides static images. The former method is very sensitive in detecting focal liver lesions >1 cm, but its specificity in characterization is not as good, not even with the color Doppler technique. The main differences between color Doppler sonography, with and/or without echocontrast agents, and contrast-enhanced (Gadolinium chelates) dynamic magnetic resonance imaging in focal liver lesions can be summarized as follows: (1) magnetic resonance imaging depicts tumor vascularization only after paramagnetic contrast media injection. Enhanced images completely depend upon the contrast agent and cannot be achieved without it. In contrast, color Doppler signal is not modified by the contrast agent, it just becomes stronger. (2) Contrast-enhanced magnetic resonance signal (as well as contrast-enhanced computed tomography signal) provides more pieces of information than color Doppler signal about the flow characteristics of liver nodules—i.e. it shows not only blood flow (hyper-/hypovascular nodule), but also the interstitial spread of the agent and its wash-out. For example, hepatocellular carcinoma and focal nodular hyperplasia have similar perfusion while agent spread and wash-out decrease very quickly in the former and more slowly in the latter, except for the low decrease of the central scar. (3) Color Doppler technology improvements, higher sensitivity to slow flows and better signal/noise ratio reduce the applications of contrast-enhanced sonography in focal liver lesions because the agents modify only sensitivity and not the imaging in slow flow studies. (4) The higher cost of contrast studies is justified only in selected cases, namely treatment follow-up in the lesions with rich pretreatment vascularization. Finally, the higher cost of contrast magnetic resonance studies is justified to increase sensitivity and especially to allow lesion characterization.

Introduction. Transcranial color Doppler sonography permits the accurate assessment of intracranial arteries. The latest Doppler units, using the color and power techniques, can show even very small flow volumes (1×1 mm). Low frequency (2–2.5 MHz) and very focused transducers are used in transcranial color Doppler. The skull is a very strong barrier for ultrasounds, which requires the use of some acoustic windows like some thin portions of the skull bone or some natural skull foramina. The use of echocontrast agents in color Doppler seems to increase the applications of transcranial studies. Objective. (1) To report on transcranial color Doppler technique and findings. (2) To assess the role of contrast agents in the visualization of intracranial vessels. (3) To define the main indications of this technique. Material and methods. The temporal, the orbital and the suboccipital are the main acoustic windows used for transcranial color Doppler studies. We use phased-array transducers (2–2.5 MHz) and, preferrably, the echocontrast agent. We examined 15 patients with severe internal carotid artery stenoses after the infusion of Levovist™ (Schering AG, Berlin, Germany) suspension (8 ml at 300 mg Galactose/ml, infused at 0.5 ml/s). Results. Levovist™ infusion permitted to depict the main intracranial vessels in all cases. The middle and the anterior cerebral arteries are shown through the temporal window. The former is the main cerebral artery, it is the easiest to identify and presents the highest peak systolic velocity. The orbital window can be used to visualize the ophthalmic artery and the internal carotid artery siphon, while the vertebral and the basilar arteries are demonstrated through the suboccipital window. Discussion. We report the most important findings and discuss the main indications of transcranial color Doppler studies. In addition to flow presence and direction, the main indices of arterial flow can be measured thanks to contrast agent administration, namely the peak systolic velocity, the end diastolic velocity, the resistance index and the pulsatility index. A morphological assessment of the Willis circle can also be carried out with color and power Doppler. Functional studies can be performed to assess the residual autoregulatory function of the cerebral circle in the patients with internal carotid artery stenosis or occlusion. The development of intracranial collateral circles can also be studied in these patients. Moreover, the M1 segment of the middle cerebral artery and the internal carotid artery siphon can be demonstrated directly. Transcranial color Doppler is also a useful tool to detect vasospasm after subarachnoid hemorrhage and to monitor blood flow velocity in the middle cerebral artery during carotid endarterectomy. The assessment of blood supply to arteriovenous malformations and to intracranial neoplasms is another application. Conclusion. With reference to internal carotid stenoses, the main applications of transcranial color Doppler are the study of intracranial vessels, of intracranial arterial stenosis, of arteriovenous malformations and of Willis circle aneurysms, as well as the monitoring of blood flow velocity during carotid endarterectomy. Echocontrast agents play an important role in the visualization of intracranial vessels.

The development of noninvasive magnetic resonance imaging (MRI) techniques sensitive to the local changes of blood flow, volume, and oxygenation which accompany neuronal activation has provided the scientific community with a new and powerful tool for investigating the spatio-temporal dynamics of human brain function [1,2]. One of the most exciting application of brain mapping techniques, such as single photon emission tomography (SPET), positron emission tomography (PET), and functional MRI (fMRI) is the study of neural correlates of mental activity, such as the internal representation of sensory events or motor acts. It is still debated to what extent brain networks activated during mental rehearsal of, for instance, a visual scene or a motor sequence (visual or motor imagery) overlap those involved in the perception of visual stimuli or the preparation and execution of motor acts, respectively [3]. With regard to the motor system, the results of previous SPET and PET studies have demonstrated the activation of higher-order motor areas (such as the supplementary motor cortex) during motor imagery, whereas no change was found in the primary sensory-motor cortex [4]. However, the relatively poor spatial resolution of the employed techniques may have prevented the detection of areas characterized by less intense activation. The present study was therefore undertaken to evaluate by high-resolution fMRI the activity pattern of the perirolandic region (including pre- and postcentral gyri) during execution and imagery of a sequential motor task.

PURPOSE: To assess the potential value of magnetic resonance imaging (MRI) combined with 67Ga single-photon emission computed tomography (SPECT) versus computed tomography (CT) in the staging and in the monitoring of mediastinal malignant lymphoma. MATERIALS AND METHODS: Twenty-three patients, referred to our institute for the evaluation of lymphoma, underwent CT, 67Ga scan, and MRI between April 1993 and February 1996 at sequential intervals. The tests studied (MRI, 67Ga, and CT) were performed according to the following schedule: 1) before start of therapy; 2) after four courses of chemotherapy; and 3) 2, 6, 12, and 18 months after the end of treatment. RESULTS: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum as well as pathologic CT and pathologic signal intensity at MRI. Six months after the end of treatment full consistency was found between the results of MRI and SPECT, whereas during treatment and 2 months after the end of therapy MRI and 67Ga scan were not in agreement in nine patients. In the 23 patients in follow-up, in CT there were nine false-positive and three false-negative findings; in SPECT three false negatives; in MRI one false positive and one false negative. CONCLUSION: MRI can give morphologic information similar to CT, even superior due to multiplanarity and with major precision in the distinction between fibrosis and active disease. MRI is thus an alternative to CT. The association with SPECT allows a great diagnostic accuracy in the positive and negative predictive value.

The intensity and spatial distribution of functional activation in the left precentral and postcentral gyri during actual motor performance (MP) and mental representation [motor imagery (MI)] of self-paced finger-to-thumb opposition movements of the dominant hand were investigated in fourteen right-handed volunteers by functional magnetic resonance imaging (fMRI) techniques. Significant increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) tasks were found in a region including the anterior bank and crown of the central sulcus, the presumed site of the primary motor cortex, during both MP (mean percentage increase, 2.1%) and MI (0.8%). In the anterior portion of the precentral gyrus and the postcentral gyrus, mean functional activity levels were also increased during both conditions (MP, 1.7 and 1.2%; MI, 0.6 and 0.4%, respectively).To locate activated foci during MI, MP, or both conditions, the time course of the signal intensities of pixels lying in the precentral or postcentral gyrus was plotted against single-step or double-step waveforms, where the steps of the waveform corresponded to different tasks. Pixels significantly (r> 0.7) activated during both MP and MI were identified in each region in the majority of subjects; percentage increases in signal intensity during MI were on average 30% as great as increases during MP. The pixels activated during both MP and MI appear to represent a large fraction of the whole population activated during MP. These results support the hypothesis that MI and MP involve overlapping neural networks in perirolandic cortical areas.

10538 Background: Imaging techniques used to evaluate response during neoadjuvant chemotherapy for breast cancer include mammography (Mx), sonography (US) and MRI. This study prospectively evaluated the ability of each technique to determine pathologic response in breast cancer patients undergoing neoadjuvant chemotherapy. Methods: Forty women with operable breast cancer (T ≥ 2 cm, N0–1, M0) were treated with four cycles of anthracycline-based and taxane-based neoadjuvant chemotherapy as part of a phase II clinical trial. The longest diameter of each tumor (n = 48 neoplastic foci) was measured by Mx, US and MRI at baseline, after two cycles and after 4 cycles of chemotherapy, before surgery. Tumor size at pathology was determined and considered as gold standard of response. Differences among techniques in measuring tumor diameters were evaluated by means of t-test. Results: At baseline, US provided statistically higher measures than Mx (mean difference: 6.3 mm, p < 0.0001) or MRI (mean difference: 5.6 mm, p < 0.0001). No difference was observed between Mx and MRI (mean difference: 0.59 mm, p = 0.5). After two cycles of chemotherapy, tumor diameter measured by US was significantly longer than that measured by Mx (mean difference: 8.8 mm, p < 0.0001) and significantly shorter than that measured by MRI (mean difference: −5.1 mm, p = 0.0009). Mx provided longer measures than MRI (mean difference: 4.4 mm, p = 0.0034). After four cycles of chemotherapy, US provided significantly shorter measures than Mx (mean difference: 11.8 mm, p < 0.0001) and MRI (mean difference: −3.3 mm, p = 0.007), whereas tumor size measured by Mx was significantly longer than that measured by MRI (mean difference: 6.75 mm, p = 0.0027). In addition, the tumor diameter measured by the pathologist was longer than that measured by US (mean difference: 2.6 mm, p = 0.09) and significantly shorter than that measured by Mx (mean difference: −7.8 mm, p < 0.0001). No statistically significant difference was observed between MRI and pathological measures (mean difference: −1.0, p = 0.5). Conclusions: This study provides further evidence that, among imaging techniques, MRI is the best method to evaluate the tumor size after neoadjuvant chemotherapy for breast cancer. No significant financial relationships to disclose.

The applications of ultrasonography (US) in oncology have rapidly increased during the past few years. Technical improvements, development of new technologies, easy availability, and non-invasiveness are some of the reasons for the rapid diffusion of US. Nowadays a large number of malignancies, both superficial and deep-seated, can be examined by US. In order to give an overview of the present role of US in oncology it is necessary to discuss many different topics including tissue characterization, diagnostic role, staging, follow-up and future developments.

Purpose To assess how frequently foci are identified on MRI in high-risk patients, and their association with malignancy, breast density, and background parenchymal enhancement (BPE). Materials and methods In this multicentric study, two readers, in consensus, retrospectively reviewed screening breast MRI of 245 high-risk women, performed between 2009 and 2014. Eligible patients had at least two consecutive screening MRI, and a follow-up of at least 1 year after a lesion was first detected; histology was available for all suspicious findings. Breast density, BPE (both using BI-RADS lexicon), presence, and changes at follow-up for foci were evaluated. Clinical history of the patients was reviewed. Chi-square test was used to define significant correlations. Results 166 women (mean age 43 years), who underwent a median of 4 MRI (range 2–6) during the study period, were included. 68 foci were found in 58 women [34.9 %, 95 % confidence interval (CI) 28.1–42.5 %]. Foci were more frequent in dense breasts (P = 0.079) and with moderate or marked BPE (P

The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography.