Pharmacokinetics and bio-distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig.

Manufactured nanomaterials have a variety of medical applications, including diagnosis and targeted treatment of cancer. A series of experiments were conducted to determine the pharmacokinetic, biodistribution and biocompatibility of two novel magnetic nanoparticles (MNPs) in the anaesthetized pig. Dimercaptosuccinic acid (DMSA) coated superparamagnetic iron oxide nanoparticles (MF66-labelled 12 nm, core nominal diameter and OD15 15 nm); at 0.5, or 2.0 mg/kg) were injected intravenously. Particles induced a dose-dependent decrease in blood pressure following administration which recovered to control levels several minutes after injection. Blood samples were collected for a 5-h period and stored for determination of particle concentration using particle electron paramagnetic resonance (pEPR). Organs were harvested post-mortem for magnetic resonance imaging (MRI at 1.5 T field strength) and histology. OD15 (2.0 mg/kg) MNP had a plasma half-life of approximately 15 min. Both doses of the MF66 (0.5 and 2.0 mg/kg) MNP were below detection limits. MNP accumulation was observed primarily in the liver and spleen with MRI scans which was confirmed by histology. MRI also showed that both MNPs were present in the lungs. The results show that further modifications may be required to improve the biocompatibility of these particles for use as diagnostic and therapeutic agents.

Spontaneous renal artery dissection: an elusive diagnosis.

Spontaneous renal artery dissection is a rare condition with an often non-specific presentation, resulting in a challenging diagnosis for clinicians. This is the case of a 39-year-old man who presented with an acute-onset right flank pain, mild neutrophilia and sterile urine. CT of abdomen and pelvis showed a patchy hypodense area in the right kidney originally thought to represent infection. He was treated as an atypical pyelonephritis with antibiotics and fluids. When his symptoms failed to improve, a diagnosis of renal infarction was considered and CT angiogram of the aorta revealed a spontaneous renal artery dissection. He was managed conservatively with systemic anticoagulation, antihypertensive treatment and analgesia and discharged home with resolution of his symptoms and normal renal function.

Fulminant limb and retroperitoneal necrotizing fasciitis in a 15-year-old girl with Fanconi anaemia.

Necrotizing fasciitis (NF) is an uncommon soft-tissue infection in children that carries a high mortality rate. We present a 15-year-old girl with chronic pancytopenia secondary to Fanconi anaemia who developed extensive NF of the lower limb, which unfortunately resulted in a fatal outcome. Immunodeficiency is a known risk factor for the development of this condition. The findings in this case demonstrate that patients with Fanconi anaemia may be susceptible to NF and that the clinical course may be more aggressive due to underlying immunosuppression. Prompt diagnosis of NF is vital in order to initiate appropriate treatment and to optimize patient outcome. Radiological investigation demonstrated extensive soft-tissue gas and destruction affecting the entire lower limb, abdominal wall and retroperitoneum, which led to timely definitive diagnosis and management.

Computed tomography diagnosed cachexia and sarcopenia in 725 oncology patients: is nutritional screening capturing hidden malnutrition?

BACKGROUND: Nutrition screening on admission to hospital is mandated in many countries, but to date, there is no consensus on which tool is optimal in the oncology setting. Wasting conditions such as cancer cachexia (CC) and sarcopenia are common in cancer patients and negatively impact on outcomes; however, they are often masked by excessive adiposity. This study aimed to inform the application of screening in cancer populations by investigating whether commonly used nutritional screening tools are adequately capturing nutritionally vulnerable patients, including those with abnormal body composition phenotypes (CC, sarcopenia, and myosteatosis). METHODS: A prospective study of ambulatory oncology outpatients presenting for chemotherapy was performed. A detailed survey incorporating clinical, nutritional, biochemical, and quality of life data was administered. Participants were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and the Nutritional Risk Index (NRI). Computed tomography (CT) assessment of body composition was performed to diagnose CC, sarcopenia, and myosteatosis according to consensus criteria. RESULTS: A total of 725 patients (60% male, median age 64 years) with solid tumours participated (45% metastatic disease). The majority were overweight/obese (57%). However, 67% were losing weight, and CT analysis revealed CC in 42%, sarcopenia in 41%, and myosteatosis in 46%. Among patients with CT-identified CC, the MUST, MST, and NRI tools categorized 27%, 35%, and 7% of them as 'low nutritional risk', respectively. The percentage of patients with CT-identified sarcopenia and myosteatosis that were categorised as 'low nutritional risk' by MUST, MST and NRI were 55%, 61%, and 14% and 52%, 50%, and 11%, respectively. Among these tools, the NRI was most sensitive, with scores <97.5 detecting 85.8%, 88.6%, and 92.9% of sarcopenia, myosteatosis, and CC cases, respectively. Using multivariate Cox proportional hazards models, NRI score < 97.5 predicted greater mortality risk (hazard ratio 1.8, confidence interval: 1.2-2.8, P = 0.007). CONCLUSIONS: High numbers of nutritionally vulnerable patients, with demonstrated abnormal body composition phenotypes on CT analysis, were misclassified by MUST and MST. Caution should be exercised when categorizing the nutritional risk of oncology patients using these tools. NRI detected the majority of abnormal body composition phenotypes and independently predicted survival. Of the tools examined, the NRI yielded the most valuable information from screening and demonstrated usefulness as an initial nutritional risk grading system in ambulatory oncology patients.

Body Composition by Computed Tomography as a Predictor of Toxicity in Patients With Renal Cell Carcinoma Treated With Sunitinib.

BACKGROUND: Sunitinib is a standard first-line option for metastatic renal cell carcinoma (mRCC). Body composition is a prognostic factor in cancer patients and patients with loss of skeletal muscle mass and fat-free mass (FFM) are prone to dose-limiting toxicity (DLT) during targeted drug therapy. We investigated whether body composition by computed tomography predicted DLT from sunitinib in mRCC. METHODS: Patients with clear cell mRCC receiving sunitinib (50 mg) were included. Skeletal muscle cross-sectional area at L3 was measured by computed tomography. Sarcopenia was defined using published cutoffs. Toxicity was assessed after 4 cycles of the drug. RESULTS: Fifty-five patients (43 male), mean age 64 years were included. Overall, 33% (N=18) of all patients were sarcopenic and of these 12.7% (N=7) were sarcopenic and overweight or obese. DLT occurred in <6 months in 53% of patients (44% male vs. 83% female) and those who experienced DLT were older (68 vs. 60 y), had a lower skeletal muscle index (51.7 vs. 59.4 cm/m), a lower FFM (51.4 vs. 57.7 kg), and received a higher drug dose in mg/kg FFM (0.9 vs. 0.8). Patients with the lowest compared with the highest measurements of skeletal muscle mass experienced more DLT, respectively, 92% versus 57% and experienced on average 5 toxicities versus 2. CONCLUSIONS: Sarcopenia is prevalent in patients with mRCC, is an occult condition in patients with normal/high body mass index, and is a significant predictor of DLT in patients receiving sunitinib. Our results highlight the potential use of baseline body composition to predict toxicity.

Volumetric quantification of global and regional left ventricular function from real-time three-dimensional echocardiographic images.

BACKGROUND: Real-time 3D echocardiographic (RT3DE) data sets contain dynamic volumetric information on cardiac function. However, quantification of left ventricular (LV) function from 3D echocardiographic data is performed on cut-planes extracted from the 3D data sets and thus does not fully exploit the volumetric information. Accordingly, we developed a volumetric analysis technique aimed at quantification of global and regional LV function. METHODS AND RESULTS: RT3DE images obtained in 30 patients (Philips 7500) were analyzed by use of custom software based on the level-set approach for semiautomated detection of LV endocardial surface throughout the cardiac cycle, from which global and regional LV volume (LVV)-time and wall motion (WM)-time curves were obtained. The study design included 3 protocols. In protocol 1, time curves obtained in 16 patients were compared point-by-point with MRI data (linear regression and Bland-Altman analyses). Global LVV correlated highly with MRI (r=0.98; y=0.99x+2.3) with minimal bias (1.4 mL) and narrow limits of agreement (+/-20 mL). WM correlated highly only in basal and midventricular segments (r=0.88; y=0.85x+0.7). In protocol 2, we tested the ability of this technique to differentiate populations with known differences in LV function by studying 9 patients with dilated cardiomyopathy and 9 normal subjects. All calculated indices of global and regional systolic and diastolic LV function were significantly different between the groups. In protocol 3, we tested the feasibility of automated detection of regional WM abnormalities in 11 patients. In each segment, abnormality was detected when regional shortening fraction was below a threshold obtained in normal subjects. The automated detection agreed with expert interpretation of 2D WM in 86% of segments. CONCLUSIONS: Volumetric analysis of RT3DE data is clinically feasible and allows fast, semiautomated, dynamic measurement of LVV and automated detection of regional WM abnormalities.

Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia.

A 15-year-old girl with a recent diagnosis of acute lymphoblastic leukaemia was admitted to hospital with pancytopaenia after having received high-dose intrathecal methotrexate 1 day prior. During the next week she had intermittent episodes of alternating hemiparesis associated with speech arrest lasting minutes to hours at a time. The episodes were not associated with altered level of consciousness or headache. MRI of the brain showed features consistent with methotrexate encephalopathy. This report discusses the typical clinical and radiological features of methotrexate neurotoxicity in addition to differential diagnoses and the proposed pathophysiological mechanisms.

Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel.

BACKGROUND: Body composition may influence clinical outcomes of certain chemotherapeutic agents. We examined the prognostic significance of skeletal muscle mass and adipose tissue on docetaxel toxicity and overall survival in patients with metastatic castrate resistant prostate cancer (mCRPC). METHODS: A retrospective review of patients medical records with mCRPC, treated with docetaxel was conducted. Body composition parameters (skeletal muscle mass, muscle attenuation [MA], visceral and subcutaneous adipose tissue) were measured at L3 by computed tomography (CT) and defined using previously established cut points. Toxicity profile was assessed after 3 cycles of the drug and graded according to the National Cancer Institute Common Toxicity Criteria (version 4). Overall survival was analysed. RESULTS: Overall 63 patients, mean age 69 years (SD 8.3), were included. Sarcopenia was present in 47% (n = 30) and of these 26.7% (8/30) were sarcopenic obese. Common toxicities (all grades) observed included fatigue (80.9%), pain (46%), and constipation (34.9%). DLT occurred in 22 (34.9%) patients; of these 10 patients (15.8%) experienced dose reductions and 12 patients (19%) experienced dose terminations. Measurements of adiposity were not predictive of DLT, however 59.1% patients who had a combination of both sarcopenia and low MA experienced DLT compared to 29.3% of patients without sarcopenia and low MA (p = 0.021). Skeletal muscle index and MA were significantly lower in patients who experienced neutropenia (grade I-II) (46.5 cm2/m2 vs. 51.2 cm2/m2, p = 0.005) compared to their counterparts (24.6 HU vs. 32.2 HU, p = 0.044). Neither sarcopenia nor sarcopenic obesity was associated with overall survival. In multivariate analysis, BMI ≥25 kg/m2 (HR: 0.349, CI: 0.156-0.782, p = 0.010) was a significant predictor of longer overall survival and both visceral fat index ≥ median 58.7 cm2/m2 (HR: 2.266 CI: 1.066-4.814, p = 0.033) and anaemia (HR: 2.81, CI: 1.297-6.091, p = 0.009) were significant predictors of shorter overall survival. CONCLUSIONS: Sarcopenia and low MA are associated with neutropenia (grade I-II). Furthermore, presence of anaemia, high volume of visceral fat and BMI <25 kg/m2 are associated with reduced survival in patients with castrate resistant prostate cancer being treated with docetaxel chemotherapy.

Fast measurement of left ventricular mass with real-time three-dimensional echocardiography: comparison with magnetic resonance imaging.

BACKGROUND: Left ventricular (LV) mass is an important predictor of morbidity and mortality, especially in patients with systemic hypertension. However, the accuracy of 2D echocardiographic LV mass measurements is limited because acquiring anatomically correct apical views is often difficult. We tested the hypothesis that LV mass could be measured more accurately from real-time 3D (RT3D) data sets, which allow offline selection of nonforeshortened apical views, by comparing 2D and RT3D measurements against cardiac MR (CMR) measurements. METHODS AND RESULTS: Echocardiographic imaging was performed (Philips 7500) in 21 patients referred for CMR imaging (1.5 T, GE). Apical 2- and 4-chamber views and RT3D data sets were acquired and analyzed by 2 independent observers. The RT3D data sets were used to select nonforeshortened apical 2- and 4-chamber views (3DQ-QLAB, Philips). In both 2D and RT3D images, LV long axis was measured; endocardial and epicardial boundaries were traced, and mass was calculated by use of the biplane method of disks. CMR LV mass values were obtained through standard techniques (MASS Analysis, GE). The RT3D data resulted in significantly larger LV long-axis dimensions and measurements of LV mass that correlated with CMR better (r=0.90) than 2D (r=0.79). The 2D technique underestimated LV mass (bias, 39%), whereas RT3D measurements showed only minimal bias (3%). The 95% limits of agreement were significantly wider for 2D (52%) than RT3D (28%). Additionally, the RT3D technique reduced the interobserver variability (37% to 7%) and intraobserver variability (19% to 8%). CONCLUSIONS: RT3D imaging provides the basis for accurate and reliable measurement of LV mass.

Lhermitte's phenomenon and platinum, beware of latency.

BACKGROUND: Lhermitte's sign (LS) is characterized by electric shock-like sensations, spreading along the spine in a cervico-caudal direction and into the arms and legs. It is felt upon flexion of the neck and reflects a myelopathy resulting from damage to sensory axons at the dorsal columns of the cervical spinal cord. In patients with cancer, LS can occur due to direct tumour involvement of the spine or in relation to radiotherapy. Chemotherapy-related LS has only rarely been reported. CASE REPORT: We present the case of a 44-year-old patient treated with platinum- and etoposide-based chemotherapy for metastatic seminoma, who subsequently developed severe disabling LS. The severity and duration of LS in this case exceeds prior reports. We review the literature on chemotherapy-related LS and discuss the practice implications. CONCLUSION: Neuropathy and LS related to cisplatin-based chemotherapy can result in significant adverse effects. Raised awareness of this complication could aid sub-phenotyping of the population most at risk and assist strategies to avert discomfort and disability post chemotherapy.

Upper gastrointestinal obstruction secondary to aortoduodenal syndrome owing to a noninflammatory abdominal aortic aneurysm.

Aortoduodenal syndrome is a rare complication of an abdominal aortic aneurysm wherein the aneurysm sac obstructs the patient's duodenum. It presents with the symptoms of an upper gastrointestinal tract obstruction and requires surgical intervention to relieve it. Previously, gastric bypass surgery was advocated, but now aortic replacement is the mainstay of treatment. We report a case of a 67-year-old woman whose aortoduodenal syndrome was successfully managed and review the literature on this topic.

Automated interpretation of regional left ventricular wall motion from cardiac magnetic resonance images.

UNLABELLED: Magnetic resonance (MR) diagnosis of regional left ventricular (LV) dysfunction relies on visual interpretation of cine images that suffers from wide inter-observer variability, especially when performed by readers not specifically trained in the assessment of LV wall motion. Quantitative analysis tools, though widely available, are rarely used because they provide large amounts of detailed information, the interpretation of which requires additional time-consuming processing. We tested the feasibility of fast automated interpretation of regional LV function using computer analysis of this wall motion information. METHODS: Dynamic, ECG-gated, steady-state free precession short-axis images were obtained in 6-10 slices in 28 subjects (10 normal volunteers; 18 patients). Images were reviewed by an expert cardiologist who provided "gold standard" grades (normal, abnormal) for regional wall motion and, independently, by four radiologists. Same images were then analyzed using custom software. Regional fractional area changes computed in normal volunteers were used to obtain the optimal segment- and slice-specific threshold values for automated classification of regional wall motion for each patient. The levels of agreement with the "gold standard" grades were compared between the radiologists and the automated interpretation. RESULTS: While the visual interpretation required 2-5 minute per patient, the automated interpretation required < 1 sec, after endocardial border detection was complete. The automated interpretation resulted in higher sensitivity, specificity, and accuracy (84%, 77%, 79%, respectively) than the radiologists' grades (80%, 76%, 77%, respectively) and eliminated the high interobserver variability. CONCLUSION: Once the endocardial boundaries are defined, computer analysis of the regional wall motion information allows accurate, fully automated, immediate, objective and experience-independent interpretation of regional LV function.

Improved quantification of left ventricular volumes and mass based on endocardial and epicardial surface detection from cardiac MR images using level set models.

PURPOSE: The reproducibility of left ventricular (LV) volume and mass measurements based on subjective slice-by-slice tracing of LV borders is affected by image quality, and volume estimates are biased by geometric modeling. The authors developed a technique for volumetric surface detection (VoSD) and quantification of LV volumes and mass without tracing and geometric approximations. The authors hypothesized that this technique is accurate and more reproducible than the conventional methodology. METHODS: Images were obtained in 24 patients in 6 to 10 slices from LV base to apex (GE 1.5 T, FIESTA). Volumetric data were reconstructed, and endocardial and epicardial surfaces were detected using the level set approach. LV volumes were obtained from voxel counts and used to compute ejection fraction (EF) and mass. Conventional measurements (MASS Analysis) were used as a reference to test the accuracy of VoSD technique (linear regression, Bland-Altman). For both techniques, measurements were repeated to compute inter- and intra-observer variability. RESULTS: VoSD values resulted in high correlation with the reference values (EDV: r = 0.98; ESV: r = 0.99; EF: r = 0.91; mass: r = 0.98), with no significant biases (8 ml, 5 ml, 0.2% and -9 g) and narrow limits of agreement (SD: 13 ml, 10 ml, 6% and 9 g). Inter-observer variability of the VoSD technique was lower (range 3 to 5%) than that of the reference technique (5 to 11%; p < 0.05). Intra-observer variability was also lower (1 to 3% vs. 7 to 10%; p < 0.05). CONCLUSION: VoSD technique allows accurate measurements of LV volumes, EF, and mass, which are more reproducible than the conventional methodology.

Improved semiautomated quantification of left ventricular volumes and ejection fraction using 3-dimensional echocardiography with a full matrix-array transducer: comparison with magnetic resonance imaging.

Our goals were to: (1) develop a technique for 3-dimensional (3D) direct, model-independent quantitative assessment of left ventricular (LV) volume and ejection fraction based on semiautomated detection of LV endocardial surface from transthoracic near real-time full matrix-array 3D echocardiographic (FM3DE) imaging; (2) evaluate the accuracy of LV volumes obtained with this technique, using cardiac magnetic resonance imaging (MRI) measurements as the reference for comparison; and (3) determine the effects of contrast enhancement on the accuracy of FM3DE measurements. A total of 46 patients underwent 2-dimensional echocardiography, FM3DE, and cardiac MRI. End-diastolic volume, end-systolic volume, and ejection fraction were derived from endocardial borders manually traced from 2-dimensional echocardiographic images and from semiautomatically detected LV cavity from FM3DE data. In 14 patients, FM3DE was also acquired with contrast. All measurements were compared with MRI values using linear regression and Bland-Altman analyses. FM3DE was feasible in 44 of 46 patients with LV volumes < 345 mL. LV volumes and ejection fraction computed from FM3DE resulted in higher levels of agreement with MRI than conventional 2-dimensional echocardiography, with lower interobserver variability. With contrast enhancement, FM3DE significantly underestimated LV volumes and showed increased interobserver variability. Semiautomated LV endocardial surface detection from FM3DE images is feasible and results in fast and accurate assessment of LV function.

Enteroclysis and computed tomography enteroclysis.

Enteroclysis, the most detailed radiologic examination of the small bowel, can be a challenge for both patient and radiologist. This article broadly outlines the principal technical features of the standard enteroclysis procedure and discusses its diagnostic advantages and indications, as well as its limitations and difficulties. A comparative assessment of computed tomography-enteroclysis and the emerging magnetic resonance adaptation complements the survey of current approaches to radiologic small bowel diagnostics.

Evidence-based radiology: how to quickly assess the validity and strength of publications in the diagnostic radiology literature.

The aim of this study was to show how evidence-based medicine (EBM) techniques can be applied to the appraisal of diagnostic radiology publications. A clinical scenario is described: a gastroenterologist has questioned the diagnostic performance of magnetic resonance cholangiopancreatography (MRCP) in a patient who may have common bile duct (CBD) stones. His opinion was based on an article on MRCP published in "Gut." The principles of EBM are described and then applied to the critical appraisal of this paper. Another paper on the same subject was obtained from the radiology literature and was also critically appraised using explicit EBM criteria. The principles for assessing the validity and strength of both studies are outlined. All statistical parameters were generated quickly using a spreadsheet in Excel format. The results of EBM assessment of both papers are presented. The calculation and application of confidence intervals (CIs) and likelihood ratios (LRs) for both studies are described. These statistical results are applied to individual patient scenarios using graphs of conditional probability (GCP). Basic EBM principles are described and additional points relevant to radiologists discussed. Online resources for EBR practice are identified. The principles of EBM and their application to radiology are discussed. It is emphasized that sensitivity and specificity are point estimates of the "true" characteristics of a test in clinical practice. A spreadsheet can be used to quickly calculate CIs, LRs and GCPs. These give the radiologist a better understanding of the meaning of diagnostic test results in any patient or population of patients.

Update on magnetic resonance cholangiopancreatography.

MRCP is a useful tool in the diagnosis of a wide variety of pathologic entities including congenital anomalies, biliary obstruction and stricture, biliary calculi, pancreatitis, neoplasms, and trauma. ERCP and MRCP both have important roles in the management of patients with suspected pancreaticobiliary disease. Knowledge of the advantages and disadvantages of each technique is needed to determine the appropriate work-up of patients with these pathologies.

Automated knowledge-guided segmentation of colonic walls for computerized detection of polyps in CT colonography.

PURPOSE: We have developed a novel automated technique for segmenting colonic walls for the application of computer-aided polyp detection in CT colonography. In particular, the technique was designed to minimize the presence of extracolonic components, such as small bowel, in the segmented colon. METHODS: The segmentation technique combines an improved version of our previously reported anatomy-oriented colon segmentation technique with a colon-based analysis step that performs self-adjusting volume-growing within the colonic lumen. Extracolonic components are eliminated by intersecting of the resulting two segmentations, so that the colonic walls remain in the intersection. The technique was evaluated on 88 CT colonography datasets. The colon segmentations were evaluated subjectively by four radiologists, as well as objectively by performance of an automated polyp detection on the segmentation. For comparison, the tests were also performed for the anatomy-oriented colon segmentation technique. RESULTS: On average, the technique covered 98% of the visible colonic walls. Approximately 50% of the extracolonic components remaining in the anatomy-oriented segmentation were removed, but 10-15% of the segmentation still contained extracolonic components. The dataset-based false-positive rate of the automated polyp detection was improved by 10% without compromising the 100% case-based sensitivity, and the case-based false-positive rate was improved by 15% over the previous false-positive rate. CONCLUSIONS: The technique segments practically all of the colonic walls in the region of diagnostic quality with a large reduction in the amount of extracolonic components over our previously used technique. The new segmentation improves the specificity of our computer-aided polyp detection scheme significantly without any degradation in detection sensitivity.