Imaging features of the evolving patterns of metastatic prostate cancer.

The pattern of metastases in prostate cancer (PC) is evolving. Increased use of imaging, newer imaging techniques with higher sensitivity for disease detection and patients receiving multiple lines of novel therapies with increased life expectancy are likely to be contributory. Awareness of metastatic disease patterns improves early diagnosis, accurate staging, and initiation of appropriate therapy, and can inform prognostic information and anticipate potential disease complications. The aim of this review is to document the spectrum of metastases in PC including emerging and unusual patterns, and to highlight the role of novel imaging including prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET) and whole-body magnetic resonance imaging (WB-MRI) to improve diagnostic and response assessment accuracy.

Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Whole-body MRI: a practical guide for imaging patients with malignant bone disease.

Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease.

Dichloroacetate induces autophagy in colorectal cancer cells and tumours.

BACKGROUND: Dichloroacetate (DCA) has been found to have antitumour properties. METHODS: We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting, electron microscopy, (1)H and hyperpolarised (13)C-magnetic resonance spectroscopy. RESULTS: Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo. We observed increased production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6 ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1 following DCA treatment. Steady-state lactate excretion and the apparent hyperpolarised [1-(13)C] pyruvate-to-lactate exchange rate (k(PL)) were decreased in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady-state lactate excretion and k(PL) returned to, or exceeded, control levels in cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH. Reduced k(PL) with DCA treatment was found in HT29 tumour xenografts in vivo. CONCLUSIONS: DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on cessation of treatment.

Measurement reproducibility of perfusion fraction and pseudodiffusion coefficient derived by intravoxel incoherent motion diffusion-weighted MR imaging in normal liver and metastases.

OBJECTIVE: To determine the measurement reproducibility of perfusion fraction f, pseudodiffusion coefficient D and diffusion coefficient D in colorectal liver metastases and normal liver. METHODS: Fourteen patients with known colorectal liver metastases were examined twice using respiratory-triggered echo-planar DW-MRI with eight b values (0 to 900 s/mm(2)) 1 h apart. Regions of interests were drawn around target metastasis and normal liver in each patient to derive ADC (all b values), ADC(high) (b values ≥ 100 s/mm(2)) and intravoxel incoherent motion (IVIM) parameters f, D and D by least squares data fitting. Short-term measurement reproducibility of median ADC, ADC(high), f, D and D values were derived from Bland-Altman analysis. RESULTS: The measurement reproducibility for ADC, ADC(high) and D was worst in colorectal liver metastases (-21 % to +25 %) compared with liver parenchyma (-6 % to +8 %). Poor measurement reproducibility was observed for the perfusion-sensitive parameters of f (-75 % to +241 %) and D (-89 % to +2,120 %) in metastases, and to a lesser extent the f (-24 % to +25 %) and D (-31 % to +59 %) of liver. CONCLUSIONS: Estimates of f and D derived from the widely used least squares IVIM fitting showed poor measurement reproducibility. Efforts should be made to improve the measurement reproducibility of perfusion-sensitive IVIM parameters.

Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging.

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Dynamic contrast-enhanced MRI of neuroendocrine hepatic metastases: A feasibility study using a dual-input two-compartment model.

Neuroendocrine hepatic metastases exhibit various contrast uptake enhancement patterns in dynamic contrast-enhanced MRI. Using a dual-input two-compartment distributed parameter model, we analyzed the dynamic contrast-enhanced MRI datasets of seven patient study cases with the aim to relate the tumor contrast uptake patterns to parameters of tumor microvasculature. Simulation studies were also performed to provide further insights into the effects of individual microcirculatory parameter on the tumor concentration-time curves. Although the tumor contrast uptake patterns can be influenced by many parameters, initial results indicate that hepatic blood flow and the ratio of fractional vascular volume to fractional interstitial volume may potentially distinguish between the patterns of neuroendocrine hepatic metastases.

Prospective assessment of MRI for imaging retroperitoneal metastases from testicular germ cell tumours.

AIM: To determine the sensitivity of magnetic resonance imaging (MRI) in the detection of retroperitoneal lymph nodes in patients with testicular germ cell tumours (TGCT). METHODS AND MATERIALS: A prospective study of 52 patients (mean age 34 years, range 18-54 years) was performed. Imaging of the retroperitoneum was performed using multidetector computed tomography (CT) and 1.5 T MRI systems. The CT and MRI images were read independently by three observers. The number, size, and site of enlarged nodes (> or =10 mm maximum short axis diameter) were recorded. Retroperitoneal nodal detection on MRI was compared to CT. RESULTS: Twenty-two (42%) of the 52 patients had no retroperitoneal disease; in remaining 30 patients 51 enlarged nodes were identified. On a per patient basis readers 1, 2, and 3 identified nodal disease in 28 of 29, 29 of 30, and 24 of 30 patients, respectively, using MRI compared to CT. Thus for experienced radiologists (readers 1 and 2) MRI is comparable to CT for nodal detection (i.e., this study excludes MRI being inferior to CT with 80% power and 5% type 1 error). CONCLUSION: MRI offers an alternative method for staging the retroperitoneum in young patients being followed for TGCT and has the major advantage of avoiding exposure to ionizing radiation.

Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes.

INTRODUCTION: To assess if parameters in intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) can be used to evaluate early renal fibrosis in a mouse model of diabetic nephropathy. MATERIALS & METHODS: In a population of 38 male CD1 mice (8weeks old, 20-30g), streptozotocin induced diabetes was created in 20 mice via a single intraperitoneal injection of streptozotocin at 150mg/kg, while 18 mice served as control group. IVIM parameters were acquired at 0, 12 and 24weeks after injection of streptozotocin using a range of b values from 0 to 1200s/mm2. DTI parameters were obtained using 12 diffusion directions and lower b values of 0, 100 and 400s/mm2. DTI and IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of the right kidney was performed in all mice. Results were analyzed using an unpaired t-test with P<0.05 considered statistically significant. RESULTS: Renal cortex fractional anisotropy (FA) was significantly lower in the diabetes group at week 12 as compared with the control group. Renal cortex apparent diffusion coefficient and tissue diffusivity were significantly higher in the diabetes group at week 12 compared with the control group at 12weeks. Blood flow was significantly decreased at the renal medulla at 24weeks. Histopathological analysis confirmed fibrosis in the diabetes group at 24weeks. CONCLUSION: FA is significantly reduced in diabetic nephropathy. FA might serve a potential role in the detection and therapy monitoring of early diabetic nephropathy.

Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging.

The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion-weighted MRI (DWI) fails to account for differential T 2 s in the model compartments, resulting in overestimation of pseudodiffusion fraction f. An extended model, T2-IVIM, allows removal of the confounding echo-time (TE) dependence of f, and provides direct compartment T 2 estimates. Two consented healthy volunteer cohorts (n = 5, 6) underwent DWI comprising multiple TE/b-value combinations (Protocol 1: TE = 62-102 ms, b = 0-250 mm-2s, 30 combinations. Protocol 2: 8 b-values 0-800 mm-2s at TE = 62 ms, with 3 additional b-values 0-50 mm-2s at TE = 80, 100 ms; scanned twice). Data from liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model using all data. Repeat-measures coefficients of variation were assessed for Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1) demonstrated apparent f increasing with longer TE: 22.4 ± 7% (TE = 62 ms) to 30.7 ± 11% (TE = 102 ms); T2-IVIM model fitting accounted for all data variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates (IVIM: 27.9 ± 6%, T2-IVIM: 18.3 ± 7%), as well as T 2 = 42.1 ± 7 ms, 77.6 ± 30 ms for true and pseudodiffusion compartments, respectively. A reduced Protocol 2 dataset yielded comparable results in a clinical time frame (11 min). The confounding dependence of IVIM f on TE can be accounted for using additional b/TE images and the extended T2-IVIM model.

Use of the temporal median and trimmed mean mitigates effects of respiratory motion in multiple-acquisition abdominal diffusion imaging.

Respiratory motion commonly confounds abdominal diffusion-weighted magnetic resonance imaging, where averaging of successive samples at different parts of the respiratory cycle, performed in the scanner, manifests the motion as blurring of tissue boundaries and structural features and can introduce bias into calculated diffusion metrics. Storing multiple averages separately allows processing using metrics other than the mean; in this prospective volunteer study, median and trimmed mean values of signal intensity for each voxel over repeated averages and diffusion-weighting directions are shown to give images with sharper tissue boundaries and structural features for moving tissues, while not compromising non-moving structures. Expert visual scoring of derived diffusion maps is significantly higher for the median than for the mean, with modest improvement from the trimmed mean. Diffusion metrics derived from mono- and bi-exponential diffusion models are comparable for non-moving structures, demonstrating a lack of introduced bias from using the median. The use of the median is a simple and computationally inexpensive alternative to complex and expensive registration algorithms, requiring only additional data storage (and no additional scanning time) while returning visually superior images that will facilitate the appropriate placement of regions-of-interest when analysing abdominal diffusion-weighted magnetic resonance images, for assessment of disease characteristics and treatment response.

First MRI application of an active breathing coordinator.

A commercial active breathing coordinator (ABC) device, employed to hold respiration at a specific level for a predefined duration, was successfully adapted for magnetic resonance imaging (MRI) use for the first time. Potential effects of the necessary modifications were assessed and taken into account. Automatic MR acquisition during ABC breath holding was achieved. The feasibility of MR-ABC thoracic and abdominal examinations together with the advantages of imaging in repeated ABC-controlled breath holds were demonstrated on healthy volunteers. Five lung cancer patients were imaged under MR-ABC, visually confirming the very good intra-session reproducibility of organ position in images acquired with the same patient positioning as used for computed tomography (CT). Using identical ABC settings, good MR-CT inter-modality registration was achieved. This demonstrates the value of ABC, since application of T1, T2 and diffusion weighted MR sequences provides a wider range of contrast mechanisms and additional diagnostic information compared to CT, thus improving radiotherapy treatment planning and assessment.

Metastatic intramammary lymph nodes as the primary presenting sign of breast cancer.

Intramammary lymph nodes (IMLNs) are not uncommon, and are likely to be more frequently identified with the wider use of mammography and breast ultrasound. IMLNs could be invaded by breast cancer influencing the prognosis and the management of patients. The aim of this study is to present the very rare phenomenon of metastatic involvement of these nodes from an occult breast cancer.

Benign metastasizing leiomyoma with intracaval leiomyomatosis.

We present an unusual case of benign metastasizing leiomyoma in association with intracaval leiomyomatosis. To our knowledge, this is the first reported case of metastasizing leiomyoma with coexistent intravenous leiomyomatosis (IVL). Magnetic resonance imaging is useful for the diagnosis of pelvic and caval IVL.

Distribution patterns of inflammatory sinonasal diseases.

BACKGROUND/AIM OF STUDY: There has been an increase in the demand for coronal sinus CT scan since the introduction of functional endoscopic sinus surgery; as the information provided by the scans assist the surgeon in the pre-operative plannings. Babbel and colleagues had demonstrated five distinctive patterns of recurring inflammatory sinonasal disease on CT scan. The aim of this study was to evaluate the patterns in the local population and to see if there was a difference compared to the Caucasian population. METHODS AND MATERIALS: A retrospective review of 302 scans done between March 1993 and September 1995 was carried out. All scans were carried out using a 5 mm thickness to cover the posterior sinuses and a 3 mm thickness to cover the anterior sinuses. The scans were then grouped into the various patterns and an analysis was carried out comparing the differences in the patterns between the Chinese and the non-Chinese, and between the local population and the Caucasian population in Babbel's series. RESULTS: There was no significant difference between the Chinese and the non-Chinese in the distribution of the various disease patterns. When compared to the Caucasian population, the local population had more sinonasal polyposis and sphenoethmoidal recess obstruction. CONCLUSION: The smaller nasal passages of the Asians, particularly in the Chinese, could be the reason for the more prevalence of Type III and Type IV disease compared to the Caucasian population. The more constant and frequent exposure to allergens might also contribute to the increased prevalence of Type IV disease.

Diffusion-weighted imaging of the liver: an update.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is now widely used as a standard imaging sequence for evaluation of the liver. The technique is easy to implement across different MRI platforms, and results in enhanced disease detection and characterization. With careful implementation, the quantitative apparent diffusion coefficient derived shows good measurement reproducibility, which can be applied for tissue characterization, the assessment of tumour response and disease prognostication. There is now a body of evidence that highlights the relative strengths and limitations of the technique for the assessment of liver diseases. The potential for more sophisticated analysis of DW-MRI data is currently being widely investigated.

Imaging hypoxia in tumours with advanced MRI.

Tumour hypoxia results in biological alterations that leads to a more aggressive disease phenotype and is associated with resistance to treatment. In this review, we discuss current magnetic resonance imaging techniques, which can be applied to evaluate tumour hypoxia, highlighting the principles of each technique, their pre-clinical and clinical deployment, as well as their strengths and limitations. The potential to combine these techniques, and also with other imaging modalities (e.g., PET imaging) using a multiparametric approach, may further improve our understanding of the complex interaction of vascular supply, oxygen diffusion and tissue metabolism in pathogenesis of tumour hypoxia; and its reversal with treatment.

The role of pre-treatment diffusion-weighted MRI in predicting long-term outcome of colorectal liver metastasis.

OBJECTIVE: To determine the prognostic value of pre-treatment apparent diffusion coefficient (ADC) of colorectal liver metastases in predicting disease response, progression-free survival (PFS) and overall survival (OS). METHODS: We retrospectively reviewed 102 patients who underwent pre-treatment diffusion-weighted MRI using a breath-hold (b=0, 150, 500) or a free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0-500) and mean flow-insensitive ADC (ADChigh) values (breath-hold: b=150 and 500; free-breathing: b=100 and 500) of up to three hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumour response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 12 weeks after treatment. Associations between tumour response, ADC values and clinical/laboratory parameters were examined by one-way analysis of variance. The relationship of ADC with PFS and OS was determined by Kaplan-Meier analysis. RESULTS: 62 patients responded to chemotherapy at 12 weeks. The pre-treatment mean ADC and mean ADChigh were higher in the non-responding group than in the responding group (1.55 vs 1.36, p=0.033; 1.40 vs 1.16, p=0.024). However, the PFS and OS of the two groups of patients stratified by the median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statistically significant. By multivariate Cox regression analysis, patients with ≤2 metastases and response to chemotherapy showed better PFS; white cell count ≤10 and surgical treatment were associated with better OS. CONCLUSION: Colorectal liver metastasis with higher pre-treatment mean ADC and mean ADChigh was associated with poorer response to chemotherapy. However, ADC and ADChigh values did not predict the patient outcome in this study cohort. ADVANCES IN KNOWLEDGE: High mean ADC values of colorectal liver metastases on pre-treatment diffusion-weighted MRI is associated with poorer response to chemotherapy.

Combining diffusion-weighted MRI with Gd-EOB-DTPA-enhanced MRI improves the detection of colorectal liver metastases.

OBJECTIVES: To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases. METHODS: 72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T(1) and T(2) weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics. RESULTS: 417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher [area under the curve (Az)=0.96, 0.97] than Gd-EOB-DTPA image set (Az=0.86, 0.89) or DW-MRI image set (Az=0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ=0.81-0.88). CONCLUSIONS: Combining DW-MRI with Gd-EOB-DTPA-enhanced T(1) weighted MRI significantly improved the detection of colorectal liver metastases.

Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI.

OBJECTIVES: The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies. METHODS: 44 whole-body MRI scans were reviewed retrospectively (coronal T(1) weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T(1) weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group. RESULTS: In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587). CONCLUSION: Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection.