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Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T1 relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R2*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives.

Saini A, Dina R, McIndoe GA, Soutter WP, Gishen P, DeSouza NM horough pretreatment evaluation is basic to the successful management of suspected adnexal masses because the nature and timing of surgery can be optimized if the nature of the lesion can be predicted. Although sonography is indisputably the primary imaging approach [1], MRI provides additional information on the composition of soft-tissue masses using differences in MR relaxation properties seen in various types of tissue [2–4]. This information is invaluable in determining the character of soft-tissue masses. In the pelvis, MRI has been shown to have a 91–93% overall accuracy for differentiating benign from malignant adnexal tumors [5] particularly when gadolinium-enhanced techniques are used [6]. This pictorial essay reviews the key differentiating MRI features of adnexal masses by correlating the MR appearances with the findings at histopathology.

Objective To evaluate pretreatment tumour volume as a predictor of survival in patients with cervical cancer using both endovaginal and external coil magnetic resonance imaging in order to achieve high spatial resolution and delineate small volume disease. Design A retrosfection case series. Setting A tertiary referral centre for gynaecological oncology. Population/Sample One hundred and six consecutive women with invasive carcinoma of the cervix underwent endovaginal and external coil magnetic resonance imaging on a 0.5-T or 1.5-T scanner. Methods T2-W FSE images, sagittal and transverse to the cervix, were obtained and tumour volume was calculated on the sagittal images by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated in accordance with normal clinical practice and their subsequent outcome was recorded. The relationships between clinical or imaging parameters and survival were assessed with Cox's proportional hazard method. Main outcome measures Disease-free survival. Results In 89 of these women, the tumour was Stage I and 88 of the 106 were treated principally by surgery. The median tumour volume was 4.75 cm3 (upper and lower quartiles 22 and 0.6). The median length of follow up of surviving patients was 223 weeks (quartiles 158 and 274 weeks). Stage, treatment type, lymphovascular space involvement, invasion of the parametrium, closeness of the excision margin, lymph node metastases, and magnetic resonance imaging measurements of tumour volume, parametrial invasion and lymph node disease were all significantly associated with survival in univariate analysis. Only magnetic resonance imaging measurement of tumour volume remained consistently and strongly associated with survival after multivariate analysis of parameters available prior to treatment (P= 0.001, Wald statistic 10.74). A receiver operating characteristic curve of tumour volume and disease-free survival confirmed the utility of this investigation and suggested that a cutoff around 13.0 cm3 would predict survival with a positive predictive value of 0.93 and a negative predictive value of 0.75. Conclusion Magnetic resonance imaging assessment of tumour volume using both an endovaginal and an external coil approach provides an accurate prediction of prognosis in cervical cancer and defines a population of women at high risk of recurrence and death. The predictive value of this investigation is superior to the clinical and histological parameters previously used. Use of this technique permits a more accurate choice of treatment options. These results suggest that it is the size of tumour burden that determines the outcome rather than invasion beyond the anatomical margins of the uterus.

The aim of this study was to obtain 1H MR spectra using magic angle spinning (MAS) techniques from punch biopsies (

The authors defined esophageal anatomy and evaluated esophageal cancer staging in a pilot group by comparing endoscopic magnetic resonance (MR) imaging results with pathologic and endoscopic ultrasonographic (US) results when available. A porcine esophagus, one volunteer, and 23 patients suspected of having esophageal cancer were imaged at 0.5 T. MR imaging was successful in 21 patients. Eight of these patients underwent esophagectomy (one after chemotherapy, which invalidated comparison with MR imaging; another did not undergo lymphadenectomy) and one underwent laparoscopy and nodal staging only; eight underwent US. When verified with pathologic staging, endoscopic MR imaging was accurate in six of seven patients (T stage) and five of six patients (N stage; nodal areas too obscured by artifact for comparison in one case). MR imaging and US results concurred in seven of eight (T stage) and five of eight (N stage) patients. No complications were observed. Endoscopic MR imaging is safe and probably comparable to endoscopic US, but with a tendency to overstage the disease.

Purpose To construct an inductively-coupled receiver coil system for use with a magnetic resonance (MR) compatible endoscope, and to evaluate its use in a pilot group of patients with esophageal cancer. Materials and Methods An inductively-coupled coil system, comprising a saddle geometry cylindrical receiver coil fitted as a sleeve around the endoscope tip and a pick-up coil housed within a channel of an MR-compatible endoscope, was designed and developed for use at 0.5 T. Twenty-three patients with esophageal cancer were recruited for MR endoscopy. In 17 cases, the endoscopic coil system was used in conjunction with an external surface coil in order to obtain information from the surrounding mediastinum. The examination took 40–50 minutes. Results MR imaging using the inductively-coupled endoscopic coil was successful in 21 cases (one failed intubation and one artifact from unrelated external source). Image artifact was largely due to respiration and global patient motion in sedated individuals undergoing endoscopy. Conclusion Inductively-coupled coil systems may be used with endoscopes to allow improved safety through increased patient-system isolation and detachability of coils and electronics for repair or replacement with coils tuned for different frequencies. J. Magn. Reson. Imaging 2003;18:131–135. © 2003 Wiley-Liss, Inc.

To compare, on high-spatial-resolution magnetic resonance (MR) images, the presence and distribution of the paravaginal fascia in continent women and in those with genuine stress incontinence (GSI) to establish its role in the pathophysiology of GSI.Eleven continent reference subjects and 10 GSI patients underwent MR imaging with a specifically designed endovaginal receiver coil. A urinary continence questionnaire and urogynecologic clinical examination had been completed. GSI was diagnosed with urodynamic tests. Paravaginal fascial tissue distribution was determined, and the paravaginal fascial volume (PFV) anteriorly associated with the urethra was measured. Retropubic urethral length (UL) in the supine position at rest was compared with its total length and expressed as a percentage ratio. Comparisons of urethral PFV and retropubic UL between reference subjects and the GSI patients were performed by means of two-sample t tests with unequal variances because data were parametric by means of the Shapiro-Francia W' test for normal data.The paravaginal fascia (connective tissue that contained venous plexus) was a consistent MR imaging feature in all women. Mean urethral PFV was 5.3 cm(3) +/- 0.6 (SD) in reference subjects compared with 3.5 cm(3) +/- 2.0 in GSI patients (P =.017). The ratio of the retropubic UL to its total length was 82.6% +/- 7.4 in reference subjects compared with 57.4% +/- 9.8 in GSI patients (P.001). There was a weak correlation between urethral PFV and retropubic UL (r = 0.46).There is a significant association between urethral PFV and continence status. GSI patients have a reduced urethral PFV, and greater than 40% of their urethral length lies below the pubis in the supine position at rest. However, the effects of age and hormonal status on urethral PFV remain to be evaluated.

Objectives To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer. Methods Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*). Results Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1 %, DDC 4.3 %, α 7.0 %, D 13.2 %, f 44.0 %, D* 165.1 %. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64 % of lesions. Conclusions The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability. Key points • DW-MRI data in ovarian cancer show deviation from mono-exponential behaviour • Parameters derived from the stretched exponential model showed good repeatability (CV 7 %) • The bi-exponential model was unsuitable because of poor parameter repeatability • The stretched exponential model showed comparable repeatability to the mono-exponential model • The extra parameter (α) provides scope for investigation of heterogeneity or response

We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45° to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials.

The objectives are determine the optimal combination of MR parameters for discriminating tumour within the prostate using linear discriminant analysis (LDA) and to compare model accuracy with that of an experienced radiologist.Multiparameter MRIs in 24 patients before prostatectomy were acquired. Tumour outlines from whole-mount histology, T2-defined peripheral zone (PZ), and central gland (CG) were superimposed onto slice-matched parametric maps. T2, Apparent Diffusion Coefficient, initial area under the gadolinium curve, vascular parameters (K(trans),Kep,Ve), and (choline+polyamines+creatine)/citrate were compared between tumour and non-tumour tissues. Receiver operating characteristic (ROC) curves determined sensitivity and specificity at spectroscopic voxel resolution and per lesion, and LDA determined the optimal multiparametric model for identifying tumours. Accuracy was compared with an expert observer.Tumours were significantly different from PZ and CG for all parameters (all p 0.001). Area under the ROC curve for discriminating tumour from non-tumour was significantly greater (p 0.001) for the multiparametric model than for individual parameters; at 90 % specificity, sensitivity was 41 % (MRSI voxel resolution) and 59 % per lesion. At this specificity, an expert observer achieved 28 % and 49 % sensitivity, respectively.The model was more accurate when parameters from all techniques were included and performed better than an expert observer evaluating these data.• The combined model increases diagnostic accuracy in prostate cancer compared with individual parameters • The optimal combined model includes parameters from diffusion, spectroscopy, perfusion, and anatominal MRI • The computed model improves tumour detection compared to an expert viewing parametric maps.

To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose.The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose-volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan.Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans.Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found.The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.

Although molecularly targeted cancer therapies have shown great promise, it is now evident that responses are dependent upon the molecular genetic context. Spatial and temporal tumour heterogeneity renders biopsy of solid tumours unsuitable for determining the genetic profile of the disease, making adaptation of appropriate therapy difficult. We have utilized the tunable optical absorption characteristic of gold nanorods to assess the potential of photoacoustics for non-invasive multiplexed molecular imaging. Gold nanorods with resonance peaks at 700nm and 900nm were functionalised with in-house antibodies ICR55 and ICR62, targeted to HER2 and EGFR transmembrane receptors, respectively. Three human squamous carcinoma cell lines (LICR-LON-HN4 expressing high HER2 and low EGFR, LICR-LON-HN3 expressing intermediate levels of HER2 and EGFR and A431 expressing high EGFR and low HER2) were incubated with the targeted nanorods for 24 hours. Cells were then incorporated as simulated tumours in tissue-like phantoms composed of 7.5% gelatin containing 0.5% Intralipid® for optical scattering and imaged at a depth of 2.5 cm, using a new clinical in-house multi-spectral photoacoustic imaging system. Images were obtained from the cell inclusions for wavelengths ranging from 710 to 950 nm at 40 nm intervals, and the mean amplitude of the photoacoustic image was computed for each wavelength, to determine their relative receptor expression levels. The molecular profile of the cells obtained using multi-wavelength photoacoustics had substantial similarity to that obtained using flow cytometry. These preliminary results confirm selective uptake of the functionalised nanorods, which reflects the cellular expression of therapeutically important oncoproteins, and give an indication of the potential of photoacoustics for multiplexed molecular profiling.

Accurate assessment of lymph node status before treatment is critical in the treatment of gynecologic cancers because the 5-year survival and treatment of women is influenced by lymph node involvement. The aims of this study were to investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission tomography (PET) to detect pelvic lymph node metastases by comparing imaging with histopathologic findings after lymph node dissection.Eighteen patients with gynecologic cancers were studied by all three imaging methods before surgery. The images were initially reviewed with routine diagnostic conditions and then, subsequently, by two observers who were unaware of the clinical and histopathologic findings of the patients. The nodal sites were split into upper (aortic to common iliac bifurcations) and lower (common iliac bifurcations to inguinal ligament) iliac chains. All observers' results were statistically analyzed with specificity, sensitivity, positive and negative predictive values, Fisher's exact test (individual observers) or chi-square test (combined observers), and Cohen's kappa test.Eight of 18 patients had lymph node metastases at histology. Findings of all three modalities agreed in full in only one patient. CT correctly revealed 10 node-negative patients, whereas MR imaging was correct in eight of these patients. (18)F-FDG PET correctly depicted one patient with lymph nodes negative for tumor. CT was the most specific imaging modality (97.0%), with MR imaging and PET rendering values of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT, 48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and 0.72 for PET.CT is the most specific modality for detecting lymph nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F-FDG in the ureters or bladder, which may mask or imitate lymph node metastases.

A coil tuned to 21.3 MHz was incorporated into a nasogastric tube and used as a marker of tube position during magnetic resonance (MR) imaging in a 0.5-T scanner. Catheter tracking was investigated with the coil used in both transmit/receive and in receive-only modes. Data acquired from this coil were overlaid on images obtained using the body coil of the scanner. Visualization of the full length of the catheter with local high signal at the tip was achieved with a temporal resolution of approximately 1 second. J. Magn. Reson. Imaging 2001;13:127-130.

Imaging plays an integral role in the diagnosis and management of ovarian cancer. The value of conventional anatomical modalities, such as ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), in the detection, characterisation and staging of ovarian pathology is widely established in clinical practice. Current advances in imaging include the supplementation of pure morphological depiction at a macroscopic level with visualisation and quantification of functional properties of tissue, in an effort to provide noninvasive biomarkers of disease activity and its response to treatment. Modalities, such as diffusion-weighted imaging (DWI), dynamic contrast-enhanced MRI (DCE-MRI), proton magnetic resonance spectroscopy (1H-MRS), [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and molecularly targeted PET radiotracers, radioimmunoscintigraphy (RIS) and near-infrared (NIR) optimal imaging, explore the microstructure, perfusion, biochemical composition and metabolism of ovarian tumours in vivo; their impact in diagnosis, surveillance and treatment planning and monitoring are mostly under investigation. This chapter reviews the functional imaging techniques employed in ovarian cancer and peritoneal carcinomatosis in the clinical and experimental setting and discusses their advantages, limitations and potential utility in improving management strategies.

Functional magnetic resonance (MR) techniques can be used to report on a variety of biological features of tumours. Techniques such as dynamic contrast-enhanced, diffusion-weighted, intrinsic susceptibility-weighted MR imaging and MR spectroscopy reflect, at a simplistic level, vascularity, cellularity, hypoxic status and metabolism, respectively, and provide a quantitative means of characterising tumours and monitoring their response to therapy. Dynamic contrast-enhanced and diffusion-weighted imaging are now increasingly used in the clinical assessment of patients with gynaecological malignancy, whereas intrinsic susceptibility-weighted MR imaging and MR spectroscopy remain within a research arena. This chapter reviews the role of functional MR techniques in the staging and follow-up of endometrial and cervical cancer and in characterising unusual uterine pathologies. Their impact on clinical decision making in uterine malignancy in the context of conventional imaging practice is discussed.

Heparins are glycosaminoglycans that, in addition to their anticoagulant activity, have interactions with growth factors and other glycoproteins. These interactions may stimulate neointimal hyperplasia when heparin is delivered locally on stents and stent-grafts. Modifying the structure of heparin to retain anticoagulant activity while minimizing these stimulatory effects on the vascular endothelium is desirable and may be achieved by understanding the relationships between the structure and function of the various parts of the heparin molecule.

Objective: To compare endovaginal with pelvic phased array coil magnetic resonance imaging (MRI) in detection of Stage I cervical carcinoma by correlating the findings with histopathology. Patients and Methods: Forty consecutive patients with Stage I cervical carcinoma confirmed histologically were studied using an endovaginal coil alone immediately followed by a pelvic phased array coil. T1-W transverse and T2-W FSE sagittal images made with each coil were analyzed independently by two radiologists noting the presence and size of a mass within the cervix and any parametrial extension or involvement of adjacent organs. Tumor volumes were measured using the electronic calliper to compute tumor area on each slice and multiplying by the slice thickness. Thirty patients underwent radical hysterectomy, one a trachylectomy, one simple hysterectomy and four extended cone biopsies. Four patients had radiotherapy to the primary tumor. Following surgery, histopathologic findings were recorded and tumor volumes measured. Results: Tumor volumes ranged from 0–106 cm3(median 1.4 cm3, mean 9 ± 19.4 cm3). Thirty-six patients had correlation of the primary site with the surgical specimen. Agreement between observers was excellent for both endovaginal (k = 0.90) and pelvic phased array (k = 0.96) techniques. Combined sensitivity and specificity for both observers of endovaginal MR imaging for detection of tumor was 96% and 70%, respectively; for pelvic phased array imaging sensitivity was substantially less at 54%. Specificity was higher at 83.7%, probably because small abnormalities were seldom visible. In patients treated surgically, early parametrial involvement in four women on endovaginal MRI was confirmed histologically in two. Pelvic phased array imaging showed early parametrial involvement in four women and was confirmed in one. Conclusion: Endovaginal MRI adds substantially to information from pelvic phased array images in the preoperative assessment of patients with early cervical cancer. J. Magn. Reson. Imaging 2000;12:1020–1026. © 2000 Wiley-Liss, Inc.

A method of fibre-optic colonoscopy with simultaneous high resolution MRI has been developed to obtain cross-sectional information of the intramural and extramural extent of lesions, for diagnostic and therapeutic purposes. An MR-compatible colonoscope with receiver coil was designed, developed and used in ex vivo studies to scan a section of large bowel in transverse and longitudinal planes with T1 and T2 weighted spin-echo sequences. In vivo five patients were followed-up after excision of large bowel cancer. The patients were three men and two women aged 50-77 years, (mean 65.6 years) who were studied on a 0.5 T scanner (Picker Asset, OH, USA). The coil and colonoscope were inserted into the rectum. After routine visual inspection of the colon, T1 weighted spin-echo images and radio-frequency spoiled gradient-echo images of the bowel wall were obtained. Ex vivo: three layers of bowel wall were identified: an intermediate to high signal-intense mucosa, a high signal intensity layer on T1 weighting which...

The potential for using pre-polarized liquids as contrast agents in vivo is investigated and the feasibility of the method demonstrated. In this study we show the enhancement obtained following intravenous delivery of pre-polarized saline into the antecubital vein of a volunteer. This form of contrast agent provides signal gain on time scales commensurate with its T(1) and allows repeated doses to be administered, thus making alternate acquisitions of data with and without enhancement practicable.

The use of a surface coil in MR imaging improves signal-to-noise ratio of adjacent tissues of interest. We therefore devised an endoanal receiver coil for imaging the anal sphincter. The probe is solid and re-usable: it comprises a saddle geometry receiver with integral tuning, matching and decoupling. It is placed in the anal canal and immobilised externally. Both in vitro and in vivo normal anatomy is identified. The mucosa is high signal intensity, the submucosa low signal intensity, the internal sphincter uniformly high signal intensity and the external sphincter low signal intensity on T1- and T2-weighted images. In females, the transverse perineal muscle bridges the inferior part of the external sphincter anteriorly. In perianal sepsis, collections and the site of the endoanal opening are identified. In early-onset fecal incontinence following obstetric trauma/surgery, focal sphincter defects are demonstrated; in late-onset fecal incontinence external sphincter atrophy is seen. In fecally incontinent patients with scleroderma, forward deviation of the anterior sphincter musculature with descent of rectal air and feces into the anal canal is noted. The extent of sphincter invasion is assessed in low rectal tumours. In children with congenital anorectal anomalies, abnormalities of the muscle components are defined using smaller-diameter coils. Such information is invaluable in the assessment and surgical planning of patients with a variety of anorectal pathologies.

Objective To assess the value of high resolution endovaginal magnetic resonance images (MRI) of the uterine cervix in planning management of early cervical cancer. Design Prospective cross-sectional study. Setting Specialist gynaecological oncology unit of a postgraduate teaching hospital. Participants Thirty nine women aged 25–76 years old (mean 42.5 years) with invasive carcinoma Stage I or IIa of the cervix. Methods A ring coil was positioned endovaginally around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset (Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences in transverse and sagittal planes with thin slices (2.5 mm) and small fields of view (12 cm). Tumour volumes were measured and any extension into adjacent organs and parametrium was noted. The patients were followed up after treatment and the outcome related to the MRI findings. Results There was one false positive and one false negative result among five Stage Ia patients being assessed for residual disease after cone biopsy or LLETZ. The MRI assessment of the size and distribution of the tumour was confirmed histologically in all 31 patients with Stage Ib or IIa disease who were treated surgically. One of these patients in whom no endocervical tumour was visible on MRI underwent radical trachelectomy. Three patients had radiotherapy as primary treatment. Patients with Stage Ib or IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3% vs 95.5%, P= 0.003). Conclusion High resolution MRI with an endovaginal coil allows precise measurement of tumour volume and identifies patients with small volume disease who might be considered for more conservative therapy. This technique also reveals early parametrial invasion that cannot be identified reliably by any other method. Early parametrial invasion in women with large tumours appears to have a very much worse prognosis.

Purpose: The objective of our study was to compare MRI of fistulas-in-ano using an endoanal coil with that using a pelvic phased array coil and to assess the value of a combined approach by correlating the findings with those at surgery. Method: Twenty consecutive patients with clinical suspicion of perianal sepsis were studied using an endoanal coil immediately followed by a phased array coil. Tl weighted and STIR images in transverse and coronal planes were made with each coil and analysed by noting the presence and site of a collection and primary track, the position of any internal opening, and subcutaneous or supralevator extension. Operative findings were similarly recorded. Results: Of 20 patients with suspected fistulas, 8 had simple fistulas, 8 had complex fistulas, and 4 had no current evidence of infection. The concordance between MR and surgery for identifying the presence and site of the collection, the primary track, and the internal opening in both simple and complex cases was superior using the endoanal coil as compared with the phased array. Both coils together reflected the findings of the endoanal coil used alone. However, for supralevator/subcutaneous extension, concordance was superior using the phased array compared with the endoanal coil, and a combined approach reflected the values of the phased array coil used alone. Conclusion: Endoanal MRI is highly sensitive in the delineation of fistulas-in-ano. In combination with phased array techniques, it provides valuable preoperative assessment in both simple and complex cases.

OBJECTIVE: The purpose of this study was to obtain high-resolution MR images of the various components of the anal sphincter complex in children who have anorectal disorders. We therefore used dedicated endoanal receiver coils for MR imaging. CONCLUSION: Our pilot study suggested that MR imaging that uses a dedicated endoanal coil may have considerable diagnostic potential in children who have anorectal disorders.

Purpose: OSI-930 is a novel, potent, oral small-molecule receptor tyrosine kinase inhibitor, predominantly against VEGF receptors (VEGFR), c-Kit, and platelet-derived growth factor receptors. A phase I trial was undertaken to determine safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and antitumor activity of OSI-930 in patients with advanced solid tumors. Experimental Design: OSI-930 was administered once or twice a day using a modified accelerated titration design. Pharmacokinetics and plasma soluble VEGFR2 (sVEGFR2) studies were undertaken. Dynamic contrast-enhanced MRI (DCE-MRI) and 2[18F]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) MTD expansion cohorts were conducted. Results: Fifty-eight patients received OSI-930 in 2 schedules; once a day schedule: 12 patients at doses up to 1,600 mg without reaching MTD; twice a day schedule: 46 patients at 400 mg (n = 7), 500 mg (n = 31), and 600 mg (n = 8). Dose-limiting toxicities were observed at 600 mg twice a day (n = 3): G3 rash (n = 2) and G4 γ-glutamyltransferase, establishing the MTD at 500 mg twice a day. Common G1–2 toxicities included fatigue, diarrhea, nausea, and rash. Antitumor responses were seen in 2 patients with advanced ovarian cancer [Response Evaluation Criteria in Solid Tumors (RECIST) partial response (PR) (n = 1); GCIG CA125 response (n = 1)]. Eleven of 19 heavily pretreated imatinib-resistant patients with gastrointestinal stromal tumors achieved RECIST stable disease (median duration: 126 days), with FDG-PET scans showing PRs in 4 of 9 patients. OSI-930 exposure increased with dose; substantial decreases in sVEGFR levels were observed with OSI-930 twice a day doses ≥400 mg, while DCE-MRI responses were shown in 4 of 6 patients. Conclusions: OSI-930 is safe and well tolerated, with pharmacokinetic–pharmacodynamic data supporting proof-of-mechanism with clinically relevant antitumor activity. Clin Cancer Res; 19(4); 909–19. ©2012 AACR.

The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics.Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion.There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion.Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

Our objective was to study the appearance of the uterus on MR images obtained during and 3 months after laser ablation of the endometrium and to determine if a correlation exists between the MR imaging findings and the subsequent clinical outcome. The appearance could then be used to guide the application of laser energy during the procedure to optimize the clinical result.Eight women 34-55 years old (mean, 42 years old) with symptoms of heavy, painful menses underwent laser ablation under epidural anesthesia. Imaging was done on a 0.5-T Picker Asset system with a pelvic phased-array receiver coil using conventional T1-weighted spin-echo, T2-weighted spin-echo, and gradient-recalled-echo sequences. Images were obtained preoperatively, after ablation of the anterior surface, after completion of the procedure, and 3 months later. Images were visually assessed for signal intensity changes in the endometrium and myometrium by two observers in conference. Images were quantitatively analyzed by measuring uterine volume and the width of the endometrium, junctional zone (JZ), and outer myometrium (OM) on the T2-weighted images. Preoperative and 3-month postoperative symptom scores including duration, amount of bleeding, and associated pain were recorded.MR images obtained immediately after treatment showed an increase in the volume of the uterus (mean, 21%). Endometrial thickness increased in five patients, and the JZ:OM ratio increased on the T2-weighted scans in six patients. The increase in the ratio probably represented myometrial edema. Two patients with persistent symptoms were treated with hysterectomy 6 weeks postoperatively. Of the remaining six patients, five showed an improvement in symptom scores after 3 months. The uterus returned to its preoperative size after 3 months in three patients, endometrial thinning was noted in two, and the JZ:OM ratio remained increased in two. The difference between the mean improvement in symptom scores at 3 months was significant in the patients with and without the endometrial swelling seen immediately after treatment. No statistically significant correlation existed between the amount of perioperative uterine swelling or the increase in JZ:OM ratio and the improvement in symptom scores at 3 months.On laser ablation of the endometrium, MR imaging showed significant immediate uterine swelling as well as an increase in the endometrial thickness and JZ:OM ratio. The presence of immediate endometrial swelling and the reduction in the JZ:OM ratio after 3 months correlated with a subsequent improvement in symptom scores. Perioperative endometrial swelling rather than myometrial changes is therefore an indicator of clinical outcome.

The high sensitivity but poor specificity of contrast enhanced magnetic resonance (MR) imaging for delineating malignant breast lesions is increasing the demand for MR guide breast biopsy. However, the poor patient access offered by conventional MR systems makes such procedures extremely difficult. We describe a method of performing breast biopsy outside the bore of the magnet using the 3-D MR imaging data. This involves a frameless stereotactic technique using an ultrasonic localizer. The position in space of the tip of a pointer with a handle which incorporates two ultrasound emitters can be tracked using an array of ultrasound detectors. MR visible marker beads (fiducials) placed on the breast and imaged at the same time are identified to the computer in relation to images of the breast. The ultrasonic localizer is used to register the position in space of the fiducials by touching them with the tip of the pointer. The image of the lesion within the breast can then be displayed in relation to the position of the tip of the pointer and the needle approach planned. Nine women with foci of enhancement on their dynamic contrast enhanced MR images underwent frameless stereotactic breast cytology. Needle placement within 2 mm of the lesion was achieved at first pass in eight out of nine (89%) cases: in one case the needle had to be re-positioned prior to sampling. This technique provides a means of targetting MR visible lesions using the MR imaging data whilst performing the procedure outside the magnet bore.

To document the apparent diffusion coefficient (ADC) of fibroglandular breast tissue in women at high-risk of developing breast cancer and investigate the relationship between ADC and breast density.Local research ethics approval was obtained. A total of 33 high-risk women including 17 BRCA1/2 mutation carriers (mean age, 43 years) and 16 women postmantle irradiation (mean age 40 years) underwent diffusion-weighted MRI between days 6 and 16 of their menstrual cycle. ADC histograms from a region of interest in fibroglandular tissue and mammographic breast density measurements were obtained. Mean, percentile ADC values (10th, 25th, 50th, 75th, 90th) and skew were compared for the two groups; ADC and mammographic breast density were correlated.Mean ADC values (×10(-6) mm(2) /s) were 2017 ± 197 in postmantle irradiated women and 1827 ± 289 in BRCA1/2 mutation carriers (P = 0.035) with significant differences at all percentiles (P0.0001) but not skew (P = 0.44). ADC values showed weak positive correlation with mammographic breast density in BRCA1/2 mutation carriers (r = 0.51, P = 0.043) but not in postmantle radiotherapy patients (r = 0.49, P = 0.13).Higher ADC values seen in fibroglandular tissue postmantle irradiation compared with BRCA1/2 mutation carriers has potential to improve tumor detection in these patients. Lack of correlation between ADC and breast density postmantle irradiation may be a result of microstructural changes.

Objective The anal sphincter was imaged with MR using an internal coil to demonstrate its anatomy, contrast enhancement patterns, and appearance in disease. Materials and methods A cylindrical saddle geometry coil was placed in the anal canal. Sixteen volunteers and 18 patients were examined. Imaging was performed on a 0.5 T Picker Asset MRI scanner in all the volunteers and nine patients and on a 1.0 T Picker HPQ Vista in nine patients. Then T1- and T2-weighted SE, T1-weighted GE and STIR images transverse to the sphincter, and T1-weighted SE images parallel to the sphincter in the coronal oblique plane were obtained. Intravenous gadopentetate dimeglumine (0.1 mmol/kg) was given to 2 normal subjects for dynamic studies and 10 patients for conventional postcontrast imaging. Results The coils were easy to insert and well tolerated and provided high spatial resolution. The internal sphincter had a higher signal intensity than the external sphincter on all sequences but particularly on STIR images. Brisk contrast enhancement of the internal sphincter was seen. Sphincteric abscesses and fistulous tracks were identified in three patients and confirmed at surgery. Sphincter defects were seen in three patients with past obstetric trauma, and these were also confirmed at surgery. Sphincter atrophy was seen in three patients with idiopathic fecal soiling. Conclusion MRI of the anal sphincter with an internal coil provides excellent visualization of normal anatomy and may be of considerable value in diagnosis.

Endoscopic laser ablation is a new treatment for benign prostatic hypertrophy. The objectives of this study were to determine the appearances of the prostate on MR images obtained during, 1 week after, and 3 months after this procedure and to determine if a correlation exists between the MR findings and the clinical outcome. Such appearances could then be used to guide the application of laser energy during the procedure in order to optimize the clinical result.Eight consecutive men 58-74 years old with symptoms of bladder outflow obstruction caused by benign prostatic hypertrophy underwent endoscopic laser ablation of the prostate under spinal or epidural anaesthesia. Imaging was done on a 0.5-T Picker Asset system with an endorectal receiver coil and conventional T1-weighted spin-echo, T2-weighted spin-echo, and gradient-recalled-echo sequences. T1-weighted magnetization transfer images were obtained in three patients. Images were obtained preoperatively, after ablation of the left-sided quadrants, immediately after completion of the procedure, and 1 week and 3 months later. Preoperative and 3-month postoperative symptom scores, peak urine flow rates, and bladder residual volumes were studied. Images were visually assessed for signal-intensity changes and the presence of cavitation by three radiologists in conference. The results were quantitatively analyzed by measuring prostatic volumes on the gradient-recalled-echo images and by measuring the width and area of regions of signal-intensity change on the T2-weighted images.MR images made immediately after treatment showed an increase in the volume of the prostate (mean, 34%) and a poorly defined, low-signal-intensity region around the urethra on the T2-weighted images in six patients. This probably represented coagulative necrosis. The prostate was smaller on MR images made 1 week after treatment, and after 3 months the prostate returned to its preoperative size. After 1 week, the low-signal-intensity periurethral region on the T2-weighted images was less obvious, and at 3 months it was replaced in four patients by a well-demarcated low-signal-intensity ring on the T2-weighted and gradient-recalled-echo images. No evidence of cavity formation in the prostate was seen on MR images in any patient. Symptom scores and peak urinary flow rates improved after 3 months, with a significant difference between the mean increase in symptom scores in the patients with and without the periurethral changes seen immediately after treatment. However, we found no significant difference between the mean increase in peak urinary flow rates in the patients with and without periurethral changes seen either immediately or at 3 months after treatment. No statistically significant correlation was found between the amount of prostatic swelling and the improvement in symptom scores or peak urine flow rates.In patients who have had laser prostatectomy, MR imaging shows significant immediate glandular swelling, which may account for the delayed improvement in symptoms reported with this technique. The presence of the periurethral changes immediately after treatment was correlated with a subsequent improvement in symptom scores. After 3 months, no cavity could be seen in the prostate. This may account for the poorer long-term clinical outcome reported with endoscopic laser ablation of the prostate compared with transurethral prostatectomy.

Conventional T1-weighted spin echo (T1WSE) and T1-weighted magnetization transfer (MT) images were obtained in 26 patients with biopsy-proven cirrhosis (nine Child's grade A, 10 Child's grade B and seven Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, seven showed evidence of subclinical hepatic encephalopathy and 15 were classified as having overt hepatic encephalopathy. Signal intensities of basal ganglia nuclei (head of caudate, putamen, globus pallidus and thalamus) and adjacent brain parenchyma were measured and contrast calculated. On T1WSE imaging, contrast measurements of the globus pallidus were significantly greater in patients with neuropsychiatric dysfunction than in those who were unimpaired (p < 0.05). This was not observed in the other basal ganglia nuclei. Patients with subclinical and overt hepatic encephalopathy could not be distinguished on the basis of contrast measurements of the globus pallidus or of any other nucleus. T1WSE contrast measurements of the globus pallidus were increased with elevations in blood ammonia levels (p < 0.05) and with the severity of liver dysfunction, when graded according to the Pugh's score (p < 0.05) Those patients with the worst liver injury (Child's grade C) had significantly greater T1WSE pallidal contrast measurements (p < 0.05) than those patients with minimal liver injury (Child's grade A). The patients with intermediate liver damage (Child's grade B) could not be distinguished from the other two groups. While MT imaging highlighted the basal ganglia and showed a correlation between globus pallidus contrast and blood ammonia levels (p < 0.05), no other relationship between MT contrast measurements and either the degree of hepatic encephalopathy or the severity of liver dysfunction was found.

Thirty six patients with a history of partial epilepsy had MRI of the brain performed with conventional T1 and T2 weighted pulse sequences as well as the fluid attenuated inversion recovery (FLAIR) sequence. Abnormalities were found in 20 cases (56%), in whom there were 25 lesions or groups of lesions. Twenty four of these lesions were more conspicuous with the FLAIR sequence than with any of the conventional sequences. In 11 of these 20 cases, lesions thought to be of aetiological importance were only seen with the FLAIR sequence. In eight this was a solitary lesion. In the other three, an additional and apparently significant lesion (or lesions) was only seen with the FLAIR sequence when another lesion had been identified with both conventional and FLAIR sequences. The 11 additional lesions or groups of lesions were seen in the hippocampus, amygdala, cortex, or subcortical and periventricular regions. No lesion was found with any pulse sequence in 16 (44%) of the original group of 36 patients. In the eight cases where a lesion was seen only with the FLAIR sequence, localisation was concordant with the electroclinical features. Two of the eight patients with solitary lesions seen only on the FLAIR sequence underwent surgery, after which there was pathological confirmation of the abnormality identified with imaging. In one patient with a congenital cavernoma, the primary lesion was best seen with a contrast enhanced T1 weighted spin echo sequence. In this selected series, the FLAIR sequence increased the yield of MRI examinations of the brain by 30%.

To assess baseline reproducibility and compare performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging versus DCE computed tomographic (CT) measures of early vascular response in the same patients treated with cediranib (30 or 45 mg daily).After institutional review board approval, written informed consent was obtained from 29 patients with advanced solid tumors who had lesions 3 cm or larger and in whom simultaneous imaging of an adjacent artery was possible. Two baseline DCE MR acquisitions and two baseline DCE CT acquisitions 7 days or fewer apart (within 14 days of starting treatment) and two posttreatment acquisitions with each modality at day 7 and 28 (±3 days) were obtained. Nonmodeled and modeled parameters were derived (measured arterial input function [AIF] for CT, population-based AIF for MR imaging; temporal sampling rate of 0.5 second for CT, 3-6 seconds for MR imaging). Baseline variability was assessed by using intra- and intersubject analysis of variance and Bland-Altman analysis; a paired t test assessed change from baseline to after treatment.The most reproducible parameters were DCE MR imaging enhancement fraction (baseline intrapatient coefficient of variation [CV]=8.6%), volume transfer constant (CV=13.9%), and integrated area under the contrast agent uptake curve at 60 seconds (CV=15.5%) and DCE CT positive enhancement integral (CV=16.0%). Blood plasma volume was highly variable and the only parameter with CV greater than 30%. Average reductions (percentage change) from baseline were consistently observed for all DCE MR imaging and DCE CT parameters at day 7 and 28 for both starting-dose groups (45 and 30 mg), except for DCE CT mean transit time. Percentage change from baseline for parameters reflecting blood flow and permeability were comparable, and reductions from baseline at day 7 were maintained at day 28.DCE MR imaging and DCE CT can depict vascular response to antiangiogenic agents with response evident at day 7. Improved reproducibility with MR imaging favors its use in trials with small patient numbers.

Magnetic resonance imaging is increasingly used to characterize tumors and its excellent soft tissue contrast informs on features such as water diffusivity, tissue vascularity (following injection of gadolinium chelates), or metabolism (MR spectroscopy). However, tissues with a very short T2 relaxation (

To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status.Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC(total) and a perfusion-insensitive ADC(high) (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated.ADC(total) and ADC(high) showed good reproducibility (r% = 17.6, 22.4). ADC(high) showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC(total) 1.46 ± 0.3 × 10(-3) mm(2)/s, ADC(high) 1.33 ± 0.3 × 10(-3) mm(2)/s) compared with the premenopausal breast (ADC(total) 1.84 ± 0.26 × 10(-3) mm(2)/s, ADC(high) 1.77 ± 0.26 × 10(-3) mm(2)/s; both P 0.001). No significant difference was seen in ADC values in relation to menstrual cycle (ADC(total) P = 0.2, ADC(high) P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC(total) P = 0.6, ADC(high) P = 0.46).ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours.• ADC values from fibroglandular breast tissue are measured reproducibly by multiple observers. • Mean ADC values were significantly lower in postmenopausal than premenopausal breast tissue. • Mean ADC values did not vary significantly with menstrual cycle. • Low postmenopausal ADC values may hinder tumour detection on DW-MRI.

To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer.Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis.Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P.001), while skew and kurtosis decreased after the third (P.001 and P = .006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy.An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer.

This study aimed to characterize changes in lipid saturation using magnetic resonance spectroscopy of sensitive (HeLa) and resistant (C33A; Me180) cervical cancer cell lines following exposure to paclitaxel to explore lipid profiles as biomarkers of drug resistance. Spectra were acquired at 11.74 T. Flow cytometry, electron, and confocal microscopy assessed cellular morphology. Western blots assessed cytoplasmic phospholipase A(2) , fatty acid synthase, and acyl-CoA synthetase1 expression. After 24 h of paclitaxel exposure,60% of cells showed mitotic arrest. At 48 h, HeLa cells showed apoptosis while C33A/Me180 cells showed normal morphology indicating resistance. MR-visible lipids increased significantly in all lines at 24 h with further increases at 48 h; resistant lines showed smaller increases than HeLa. Cytoplasmic phospholipase A(2) and fatty acid synthase levels were unchanged at 24 h and dropped at 48 h in HeLa; acyl-CoA synthetase1 was higher in Me180/C33A than in HeLa controls but did not increase significantly. The percentage of cells displaying lipid droplets increased significantly at 24 and 48 h in all lines; droplet size increased only in HeLa cells. Droplet number was3-4× greater in apoptotic compared with mitotic-arrested cells. Apoptotic cells accumulate unsaturated fatty acids in large (relative to control) droplets; resistant lines accumulated smaller droplets with less triglycerides.

This study correlates apparent diffusion coefficients (ADCs) from Diffusion-weighted Imaging (DWI) in primary ovarian tumours and their omental metastases following neoadjuvant chemotherapy with epithelial and stromal densities in order to relate them to histological composition. Eight patients underwent DWI at 1.5 T with four b-values (0, 600, 900, and 1,050 s/mm(2))at baseline and after one and three cycles of platinum-based chemotherapy. Mean ADCs were calculated at each timepoint from solid tumour at ovarian and omental sites. Specimens from 15 corresponding lesions (8 ovarian, 7 omental), obtained at interval debulking surgery, were stained immunohistochemically to quantify epithelial and stromal components. End-of-treatment ADC was correlated with epithelial and stromal densities. Longitudinal changes in ADC with treatment were compared between primary and metastatic lesions using parametric tests. No baseline differences in ADC between primary and metastatic sites were seen. Mean ADC increased significantly from baseline after both first and third cycle (P < 0.001) in both ovarian and omental lesions. ADC and total epithelial plus stromal density (lesion cellularity) were negatively correlated in ovarian lesions (r= -0.79, P=0.02) but not in omental metastases or when both sites were considered together. However, ADC and epithelial density were negatively correlated in ovarian (r=- 0.78, P=0.02) and omental lesions (r=-0.75, P=0.04) and when both sites were considered together (r=-0.77, P< 0.001). There was no significant correlation between ADC and stromal density. Thus ADC reflects mainly epithelial content in advanced ovarian cancer and is not solely a function of lesion cellularity.

Purpose The hepatocyte growth factor/c-MET axis is implicated in tumor cell proliferation, survival, and angiogenesis. ARQ 197 is an oral, selective, non–adenosine triphosphate competitive c-MET inhibitor. A phase I trial of ARQ 197 was conducted to assess safety, tolerability, and target inhibition, including intratumoral c-MET signaling, apoptosis, and angiogenesis. Patients and Methods Patients with solid tumors amenable to pharmacokinetic and pharmacodynamic studies using serial biopsies, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and circulating endothelial cell (CEC) and circulating tumor cell (CTC) enumeration were enrolled. Results Fifty-one patients received ARQ 197 at 100 to 400 mg twice per day. ARQ 197 was well tolerated, with the most common toxicities being grade 1 to 2 fatigue, nausea, and vomiting. Dose-limiting toxicities included grade 3 fatigue (200 mg twice per day; n = 1); grade 3 mucositis, palmar-plantar erythrodysesthesia, and hypokalemia (400 mg twice per day; n = 1); and grade 3 to 4 febrile neutropenia (400 mg twice per day, n = 2; 360 mg twice per day, n = 1). The recommended phase II dose was 360 mg twice per day. ARQ 197 systemic exposure was dose dependent and supported twice per day oral dosing. ARQ 197 decreased phosphorylated c-MET, total c-MET, and phosphorylated focal adhesion kinase and increased terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) staining in tumor biopsies (n = 15). CECs decreased in 25 (58.1%) of 43 patients, but no significant changes in DCE-MRI parameters were observed after ARQ 197 treatment. Of 15 patients with detectable CTCs, eight (53.3%) had ≥ 30% decline in CTCs after treatment. Stable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST), ≥ 4 months was observed in 14 patients, with minor regressions in gastric and Merkel cell cancers. Conclusion ARQ 197 safely inhibited intratumoral c-MET signaling. Further clinical evaluation focusing on combination approaches, including an erlotinib combination in non–small-cell lung cancer, is ongoing.

We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n = 17) compared with those who did not (non-progressors, n = 33).50 consecutive patients (Stage T1/2a, Gleason grade ≤ 3+4, prostate-specific antigen (PSA)15 ng ml⁻¹,50% cores positive) were imaged endorectally (baseline and 1-3 years follow-up) with T₂ weighted (T₂W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T₂W images yielded ADC(all) (b = 0-800), ADC(fast) (b = 0-300) and ADC(slow) (b = 300-800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant).Tumour and whole prostate ADC(all) and ADC(fast) were significantly reduced over time in progressors (p = 0.03 and 0.03 for tumours, respectively; p = 0.02 and 0.007 for the whole prostate, respectively). There were no significant changes in ADC over time in non-progressors. A 10% reduction in tumour ADC(all) indicated progression with a 93% sensitivity and 40% specificity (A(z) of receiver operating characteristic (ROC) curve = 0.68). Percentage reductions in whole prostate ADC(all), ADC(fast) and ADC(slow) were also significantly greater in progressors than in non-progressors (p = 0.01, 0.03 and 0.008, respectively).This pilot study shows that DW-MRI has potential for monitoring patients with early prostate cancer who opt for active surveillance.

To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values. The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.3 years) and 43 patients with metastatic and myelomatous involvement (mean age 65.5 years) were measured. In 9 volunteers diffusion weighted MRI was repeated within 7 days. b values were derived to optimise contrast between normal and pathological marrow. The mean ADC of bone marrow in younger volunteers was significantly higher than that of older volunteers. The coefficient of reproducibility was 14.8%. The ADC mean of metastatic and myeloma bone disease was $$ {1}0{54} + / - {456} \times {1}0 ^{-6} {\text{mm}}^{2}{\text{s}} ^{-1} $$ . An ADC threshold of 655 × 10−6 mm2s−1 separated normal and abnormal marrow with a sensitivity and specificity of 90% and 93% respectively. Contrast between normal and abnormal marrow was optimal at b = 1389 smm−2. The reproducibility of ADC measurements in bone is equivalent to published data for soft tissue with a high sensitivity and specificity for separating abnormal from age matched normal bone marrow. A b value of around 1,400 smm−2 is optimal for imaging bone marrow.