Development of a diffusion-weighted MRI protocol for multicentre abdominal imaging and evaluation of the effects of fasting on measurement of apparent diffusion coefficients (ADCs) in healthy liver

Objective:

To assess the effect of fasting and eating on estimates of apparent diffusion coefficient (ADC) in the livers of healthy volunteers using a diffusion-weighted MRI protocol with b-values of 100, 500 and 900 s mm⁻² in a multicentre study at 1.5 T.

Methods:

20 volunteers were scanned using 4 clinical 1.5-T MR scanners. Volunteers were scanned after fasting for at least 4 h and after eating a meal; the scans were repeated on a subsequent day. Median ADC estimates were calculated from all pixels in three slices near the centre of the liver. Analysis of variance (ANOVA) was used to assess the difference between ADC estimates in fasted and non-fasted states and between ADC estimates on different days.

Results:

ANOVA showed no difference between ADC estimates in fasted and non-fasted states (p = 0.8) nor between ADC estimates on different days (p = 0.8). The repeatability of the measurements was good, with coefficients of variation of 5.1% and 4.6% in fasted and non-fasted states, respectively.

Conclusion:

There was no significant difference in ADC estimates between fasted and non-fasted measurements, indicating that the perfusion sensitivity of ADC estimates obtained from b-values of 100, 500 and 900 s mm⁻² is sufficiently low that changes in blood flow in the liver after eating are undetectable beyond the variability in the measurements.

Advances in knowledge:

Assessment of the effect of prandial state on ADC estimates is critical, in order to determine the appropriate patient preparation for biological validation in clinical trials.Diffusion-weighted MRI (DW-MRI) has wide application in oncology with several studies indicating its utility for characterizing liver lesions.^1–6 DW-MRI is a relatively simple technique, which does not require administration of exogenous contrast agents, and provides qualitative and quantitative information. It measures the thermal mobility of water molecules in biological tissues, which is affected by their interactions with cell membranes and by the presence of macromolecules. The biexponential behaviour of the DW-MRI signal, which is characterized by a steep attenuation at low b-values (0–100 s mm⁻²) and a slower attenuation at higher b-values (>100 s mm⁻²), is believed to represent the perfusion of the blood in the microcirculatory vessels (so-called pseudodiffusion), and the diffusion of the extracellular water molecules, respectively.⁷ Until recently, most clinical studies have used a monoexponential curve fitted to b-values, 0–1000 s mm⁻² to estimate the apparent diffusion coefficient (ADC), where the reliability of this ADC estimation is affected by the lower b-values, thus including the influence from the pseudodiffusion component of the signal.^1,3,5 However, there is increasing recognition of the need to exclude the lower b-values in order to eliminate the effects of perfusion, particularly in tissues such as the liver where blood flow is high.^8–10Over the past decade, several investigators have proposed and documented the importance of the addition of DW-MRI sequences to the standard MR sequences for the identification of liver lesions as well as for assessing treatment response.^1,4,5 However, in clinical trials, variability of the measurement owing to technical (multivendor platforms) and biological (physiological variations) factors remains a challenge.¹¹ It is crucial, therefore, to standardize imaging protocols for data acquisition to minimize variability and achieve as reproducible a measurement as possible. To implement diffusion-weighted (DW) imaging in a clinical trial, standardized acquisition parameters within the capability of a range of scanner types should be addressed. Furthermore, in order to ensure reduction of physiological variation, the effects of patient preparation and biological status on the measurement need to be understood. Several individual studies in the literature have attempted to investigate the effect of calorie intake on the ADC estimates of the liver.^12–14 However, no study addresses the effect of fasting or feeding on the ADC measurement in the context of a standardized multivendor acquisition protocol in a multicentre study.We therefore designed a protocol with acquisition parameters that were implemented across 1.5-T scanners from a variety of manufacturers and prospectively studied the effects of fasting on the ADC estimates in healthy livers, recording the variability in the measurement at two time points. A minimum b-value of 100 s mm⁻² was employed in estimation of ADCs in order to minimize the influence of perfusion on our measurements.     

Repeatability of quantitative metrics derived from MR diffusion tractography in paediatric patients with epilepsy

Objective:

To quantify the test–retest repeatability of mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) tractography in a cohort of paediatric patients with localization-related epilepsy.

Methods:

30 patients underwent 2 DTI acquisitions [repetition time/echo time (ms), 7000/90; flip, 90°; b-value, 1000 s mm⁻²; voxel (mm), 2 × 2 × 2]. Two observers used Diffusion Toolkit and TrackVis (www.trackvis.org) to segment and analyse the following tracts: corpus callosum, corticospinal tracts, arcuate fasciculi, inferior longitudinal fasciculi and inferior fronto-occipital fasciculi. Mean MD and mean FA were calculated for each tract. Each observer independently analysed one of the DTI data sets for every patient.

Results:

Segmentation identified all tracts in all subjects, except the arcuate fasciculus. There was a highly consistent relationship between repeated observations of MD (r = 0.993; p < 0.0001) and FA (r = 0.990; p < 0.0001). For each tract, coefficients of variation ranged from 0.9% to 2.1% for MD and from 1.5% to 2.8% for FA. The 95% confidence limits (CLs) for change ranged from 2.8% to 6% for MD and from 4.3% to 8.6% for FA. For the arcuate fasciculus, Cohen''s κ for agreement between the observers (identifiable vs not identifiable) was 1.0.

Conclusion:

We quantified the repeatability of two commonly utilized scalar metrics derived from DTI tractography. For an individual patient, changes greater than the repeatability coefficient or 95% CLs for change are unlikely to be related to variability in their measurement.

Advances in knowledge:

Reproducibility of these metrics will aid in the design of future studies and might one day be used to guide management in patients with epilepsy.Epilepsy is a common neurological condition defined by recurrent unprovoked seizures that affects 1% of the population, including 1 in 200 children.^1,2 Unlike in adults, developmental lesions predominate as the source of seizures in children; in particular, focal cortical dysplasia is the most common anatomical substrate for intractable epilepsy in the paediatric population.³ A high proportion of epilepsies occurring in the setting of cortical malformations are pharmacoresistant,⁴ highlighting the importance of alternative management strategies. In appropriately selected patients who fail medical management, surgical resection of the dysplastic cortex can be curative. In such cases, pre-operative identification and complete resection of the structural lesion are important prognostic factors.^5,6 Decision making surrounding the pursuit of invasive alternatives is rarely straightforward, however, and in practice relies heavily on supplementary information provided by novel diagnostic techniques.Although surgical management is an attractive option for many patients with focal seizures, medical therapy continues to be adopted as the “safe” strategy in a significant portion of this population. However, there is good evidence to suggest that ongoing seizures and treatment with antiseizure medication might be associated with progressive alterations in white matter integrity.^7–9 Furthermore, these same ongoing processes can contribute to progressive functional decline.^10,11 As such, the ability to confidently identify progression of network alterations in an individual patient with epilepsy, whether on the basis of ongoing seizure activity, antiseizure medication or both, would be of great value to informed decision making surrounding potential surgical intervention.With the advent of diffusion-weighted imaging (DWI), the microstructural properties of a tissue of interest can be non-invasively probed at a spatial scale that is otherwise unattainable using even the most advanced structural MR techniques. Diffusion tensor imaging (DTI) is a variation on the theme of DWI, which quantifies water motion in three orthogonal dimensions and, therefore, is better able to capture the anisotropic tendencies of diffusion in highly organized tissues, such as cerebral white matter.¹² Numerous scalar metrics can be derived from the tensor; the most commonly referenced are mean diffusivity (MD) and fractional anisotropy (FA). MD provides a measure of overall incoherent motion within a voxel without regard for direction and reflects tissue organization at the cellular level.¹³ Increased MD is a common manifestation of white matter pathology of diverse aetiology.^14–16 By contrast, FA provides a measure of the degree to which a single direction of water motion dominates overall diffusivity in a voxel. As such, FA has been shown to be a relatively robust measure of white matter integrity.^17–21 Diffusion tractography is an extension of DTI in which the directional tendencies of water diffusion are used to create three-dimensional representations of white matter tracts based on their structural coherence.^22,23 In many instances, the functional role of the constructed pathways is at least in part known, which enables assessment of brain parenchymal abnormalities in terms of functional systems.^16,24DTI and diffusion tractography already occupy a prominent place in epilepsy research, and they are increasingly used to guide clinical management of epilepsy patients.^7,25–30 Although preliminary results are promising, a thorough understanding of the test–retest reproducibility of metrics derived from DTI will be crucial to the widespread application of this technique. Such knowledge would inform the design of both cross-sectional and longitudinal studies, including appropriate sample size selection. Furthermore, the clinical utility of such quantitative techniques will be predicated on an understanding of their intrinsic variability at the level of the individual. In particular, an understanding of what represents true difference at the individual level will be required to ascribe significance to changes in these metrics that occur in an individual patient. To date, however, the reproducibility of quantitative metrics derived from tractography has not been widely studied and, in particular, there are very few data from either the paediatric or epilepsy populations.³¹ The goal of this study, therefore, was to measure the repeatability of MD and FA derived from DTI tractography in a cohort of paediatric patients with localization-related epilepsy.     

Changes in apparent diffusion coefficients in the normal uterus during different phases of the menstrual cycle

This study investigated the apparent diffusion coefficients (ADCs) of the uterine zonal structures (myometrium, endometrium and junctional zone) among reproductive women, and their changes during the menstrual cycle. Magnetic resonance (MR) images of seven healthy females (aged 24–31 years) were obtained during the periovulatory, luteal and menstrual phases. Diffusion-weighted imaging (DWI) was performed with a single-shot echo-planar imaging (EPI) sequence in the midsagittal plane of the uterus using three b-values (b = 0, 500 or 1000 s mm⁻²). The ADC values of the three uterine zonal structures were measured on an ADC map by placing two regions of interest (ROI) on the corresponding zonal structures. The average changes of ADC values (intra-individual ADC value variation) over three menstrual phases were 0.41 × 10⁻³ mm² s⁻¹ (range, 0.08–0.91) for myometrium, 0.55 × 10⁻³ mm² s⁻¹ (0.35–0.84) for endometrium, and 0.40 × 10⁻³ mm² s⁻¹ (0.18–0.59) for the junctional zone. The ADC values for myometrium and endometrium were lower in the menstrual phase, although there was some overlap of individual values. Interindividual variation in ADC value for a given zone or phase ranged from 0.48 × 10⁻³ mm² s⁻¹ to 0.85 × 10⁻³ mm² s⁻¹. Intermeasurement variation between the two ROIs ranged from 0 to 0.48 × 10⁻³ mm² s⁻¹ per measurement. The magnitude of these variations was comparable to reported differences between malignant and non-malignant tissues. These preliminary results, from a small number of subjects, suggest that the menstrual cycle and individual variation in pre-menopausal women should be considered when interpreting the ADC values of uterine structures.Diffusion-weighted imaging (DW) is an emerging functional imaging technique that is based on the diffusion of water molecules [1]. DWI can measure the apparent diffusion coefficient (ADC) of the water in tissue, which reflects its cell density, cellular oedema and microcirculation [1, 2]. Malignant tissue tends to have low ADC values, and so ADCs are increasingly used as a quantitative parameter to distinguish malignant tissue from non-malignant tissue [3–5]. Recent studies in gynaecological imaging have reported ADC values that were lower than normal in uterine cervical cancer, endometrial cancer and leiomyosarcoma [6–8].In pre-menopausal women, T₂ weighted images of the uterus, a three-layer zonal structure, change during the menstrual cycle [9–11]. When the variation in the appearance of the uterus on T₂ weighted images and the underlying physiological changes are considered, it seems possible that there might be variation of ADCs in the normal uterus during the menstrual cycle, which could affect the baseline ADC values used in the assessment of uterine abnormalities. Thus, the purpose of this study was to investigate the ADC values of each zonal structure in the uterus among reproductive women, and their variation in three different phases of the menstrual cycle.     

Diffusion-weighted MRI in the follow-up of chronic periaortitis

Objective:

To evaluate the usefulness of diffusion-weighted MRI (DWI) for the assessment of the intraindividual follow-up in patients with chronic periaortitis (CP) under medication.

Methods:

MRI data of 21 consecutive patients with newly diagnosed untreated disease were retrospectively examined before and after medical therapy, with a median follow-up of 16 weeks. DWI parameters [b800 signal, apparent diffusion coefficient (ADC) values] of the CP and psoas muscle were analysed together with the extent and contrast enhancement. Pre- and post-treatment laboratory inflammation markers were acquired parallel to each MR examination.

Results:

Statistically significant lower b800 signal intensities (p ≤ 0.0001) and higher ADC values (p ≤ 0.0001) were observed after medical treatment within the fibrous periaortic tissue. Extent and contrast enhancement of the CP showed also a statistically significant decrease (p ≤ 0.0001) in the follow-up examinations, while the control parameters within the psoas muscle showed no differences.

Conclusion:

DWI seems to be a useful method for the evaluation of response to treatment without contrast agents. The technique may be helpful in the assessment of disease activity to guide further therapeutic strategies.

Advances in knowledge:

DWI detects significant differences in the intraindividual follow-up of CP under medical therapy.Chronic periaortitis (CP) is a proliferating fibroinflammatory disease of the perivascular retroperitoneal space and aortic wall.^1–4 Owing to adventitial inflammation, some recent theories consider CP as a large vessel vasculitis.⁵ Clinical manifestations of CP include idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm and perianeurysmal retroperitoneal fibrosis.^2,6,7 The three manifestations with very similar histopathological characteristics are distinguished by the diameter of the abdominal aorta and concomitant ureteral affection.^1,3,7Specific clinical symptoms are caused by extrinsic compression of the ureters or retroperitoneal veins, resulting in hydronephrosis, oliguria, lower extremity oedema and deep vein thrombosis.^1,8Under medical treatment with steroids, CP has a good prognosis.⁷ Today tamoxifen is suggested as a safe and effective therapeutic alternative, and immunosuppressive drugs can be considered in patients with suboptimal responses to these drugs or multiple relapses.^9–11CT and MRI are the modalities of first choice for diagnosis and follow-up of CP.^1,7,12 The fibrotic para-aortic tissue shows significant contrast uptake in gadolinium-enhanced MRI.^12–14 Dynamic contrast-enhanced MRI was suggested for the assessment of the disease activity.^15,16 However, in cases with impaired renal function (e.g. by ureteral compression), gadolinium-independent imaging methods should be preferred owing to the potential development of a nephrogenic systemic fibrosis.¹⁷Diffusion-weighted MRI (DWI) is a non-contrast MR modality that has been successfully applied for the assessment of retroperitoneal masses, inflammatory abdominal aortic aneurysms and for the differentiation between retroperitoneal fibrosis and malignant retroperitoneal neoplasms.^18–21DWI indicates restricted diffusion of water, for example caused by a high cellularity in malignant disease or active inflammation. The apparent diffusion coefficient (ADC) is a quantitative parameter for the level of restricted diffusion, which is calculated from the signals of different diffusion gradients (b-values).²²In the context of untreated CP diffusion-weighted MRI may detect restricted inflammation as a sign of high cellularity caused by active inflammation.There are no data for the evaluation of intraindividual follow-up and the response to treatment by DWI of CP so far. Therefore, the aim of the present study was to analyse differences in DWI signals during follow-up in patients with CP before and after treatment. In addition, we sought to elucidate the potential of DWI in the therapy monitoring of CP.     

Obscure gastrointestinal bleeding: diagnostic performance of 64-section multiphase CT enterography and CT angiography compared with capsule endoscopy

Objective:

To compare the diagnostic capabilities between capsule endoscopy (CE) and multislice CT (MSCT) enterography in combination with MSCT angiography for assessment of obscure gastrointestinal bleeding (OGIB).

Methods:

A total of 127 patients with OGIB were looked at in this study. 82 patients (aged 42.7 ± 19.1 years; 34 males) were assigned to receive MSCT diagnosis and 67 patients to (aged 53.9 ± 16.2 years; 28 males) receive CE diagnosis. Among them, 22 patients (aged 54.1 ± 19.1 years; 12 males) received both examinations. Oral isotonic mannitol and intramuscular injection of anisodamine were performed; non-ionic contrast (iopromide, 370 mg I ml⁻¹) was intravenously administered; and then multiphase scanning was conducted at arterial, small intestinal and portal venous phases in MSCT. The results were compared with findings of reference standards including double balloon enteroscopy, digital subtraction angiography, intraoperative pathological examination and/or clinical diagnosis.

Results:

Administration of anisodamine markedly increased the satisfaction rate of bowel filling (94.67% vs 28.57%; p < 0.001) but not the diagnostic yield (p = 0.293) of MSCT. Compared with MSCT, CE showed an improved overall diagnostic yield (68.66% vs 47.56%; p = 0.010), which was also observed in overt bleeding patients (i.e. patients with continued passage of visible blood) (76.19% vs 51.02%; p = 0.013) and in patients aged younger than 40 years of age (85% vs 51.28%; p = 0.024). However, CE had similar positive rates to MSCT (p > 0.05). Among the 22 cases in whom both examinations were conducted, CE showed no significantly different diagnostic capability compared with MSCT (p = 0.4597).

Conclusion:

Both CE and MSCT are safe and effective diagnostic methods for OGIB.

Advances in knowledge:

CE is preferred for overt bleeding or patients aged younger than 40 years. The combined use of CE and MSCT is recommended in OGIB diagnosis.Obscure gastrointestinal bleeding (OGIB), which accounts for approximately 5% of all gastrointestinal haemorrhage cases,¹ is defined as persistent or recurring gastrointestinal bleeding without an obvious aetiology after gastroduodenoscopy and colonoscopy.^2,3 Based on the presence or absence of clinically evident bleeding, OGIB could be divided into occult (no visible blood) and overt (continued passage of visible blood, such as haematemesis, melaena or haematochezia) bleeding.^3,4 OGIB frequently occurs in the small bowel and is caused by small bowel diseases such as intestinal erosions, ulcers, vascular anomaly, gastrointestinal tumours and inflammatory bowel and parasitic diseases.^5,6Multiple diagnostic techniques have been developed to elucidate the causes of OGIB. Among them, two non-invasive technologies, capsule endoscopy (CE) and multislice CT (MSCT) markedly improved the ability to determine the causes of OGIB by allowing the visualization of the gastrointestinal tract.^2,3,6 CE is able to obtain direct visualization of mucosal surface of the entire small intestine.^4,7,8 However, capsule retention remains a major risk of CE diagnosis.^4,9–11 In addition, the visual field restriction limits the value of CE in diagnosis of umbilicate or extraluminal lesions, since the small bowel is difficult to evaluate owing to its large length and tortuous course.^4,10 Conversely, MSCT, including MSCT angiography (MSCTA), MSCT enteroclysis and MSCT enterography (MSCTE), has full capacity to depict the extraintestinal lesions, owing to the combination of the advantages of enteral volume challenge with the ability of cross-sectional imaging.^4,12 Yet, substantial patient radiation exposure is one of the major disadvantages of MSCT diagnosis.^3,13 Careful preparation is also needed before examination.¹⁴ Considering that both CE and MSCT have advantages and disadvantages, a limited number of published data have compared the two diagnostic tools in patients with OGIB.^4,6,15–17 However, most of these studies did not refer to MSCTA, and apparently different results were obtained owing to the advancement of the two technologies. Thus, an updated and comprehensive comparison is required.Hence, we compared the diagnostic capability of MSCTE in combination with MSCTA with CE in patients suffering from OGIB. In this study, MSCTE and MSCTA technologies performed with a 64-slice spiral CT scanner were combined by non-contrast-enhanced scanning after oral administration of a neutral enteric contrast material (isotonic mannitol, 2.5%) and the intramuscular injection of anisodamine to restrain enterocinesia, and the following multiphase scanning at arterial, small intestinal and portal venous phases followed the intravenous infusion of non-ionic iodinated contrast material (iopromide, 370 mg I ml⁻¹). In addition, the influences of the clinical bleeding pattern and age on the diagnostic capability were also investigated.     

A change in the apparent diffusion coefficient after treatment with bevacizumab is associated with decreased survival in patients with recurrent glioblastoma multiforme

Objectives

The aim of this study was to determine the prognostic significance of changes in parameters derived from diffusion tensor imaging (DTI) that occur in response to treatment with bevacizumab and irinotecan in patients with recurrent glioblastoma multiforme.

Methods

15 patients with recurrent glioblastoma multiforme underwent serial 1.5 T MRI. Axial single-shot echo planar DTI was obtained on scans performed 3 days and 1 day prior to and 6 weeks after initiation of therapy with bevacizumab and irinotecan. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were registered to whole brain contrast-enhanced three-dimensional (3D) spoiled gradient recalled and 3D fluid attenuation inversion recovery (FLAIR) image volumes. Anatomic image volumes were segmented to isolate regions of interest defined by tumour-related enhancement (TRE) and FLAIR signal abnormality (FSA). Mean ADC and mean FA were calculated for each region. A Bland–Altman repeatability coefficient was also calculated for each parameter based on the two pre-treatment studies. A patient was considered to have a change in FA or ADC after therapy if the difference between the pre- and post-treatment values was greater than the repeatability coefficient for that parameter. Survival was compared using a Cox proportional hazard model.

Results

DTI detected a change in ADC within FSA after therapy in nine patients (five in whom ADC was increased; four in whom it was decreased). Patients with a change in ADC within FSA had significantly shorter overall survival (p=0.032) and progression free survival (p=0.046) than those with no change.

Conclusion

In patients with recurrent glioblastoma multiforme treated with bevacizumab and irinotecan, a change in ADC after therapy in FSA is associated with decreased survival.Genotypic heterogeneity within histologically indistinguishable tumours remains a major barrier to successful treatment of patients with high-grade primary brain tumours [1]. Because of this heterogeneity, only a minority of individual tumours are likely to respond to any given chemotherapeutic agent [2]. Early identification of non-responders would allow potentially more effective therapy to be instituted while minimising the morbidity and financial cost associated with prolonged, ineffective treatment. Current assessment of therapeutic efficacy relies on changes in cross-sectional area estimated weeks to months after the completion of a treatment protocol [3,4]. Unfortunately, patients with aggressive tumours may experience significant disease progression with related morbidity and mortality before therapy can be evaluated and altered using this approach. Biomarkers of treatment response that are independent of late changes in tumour volume will be crucial for optimal treatment of this patient group.Diffusion-weighted MRI (DWI) can be used to characterise early tissue microstructural changes associated with cell death [4,5]. Since parameters derived from DWI can provide a quantitative assessment of such effects, there is increasing interest in this technique as a biomarker of therapeutic efficacy. Although there is good evidence that DWI can be used to characterise treatment effects, the optimal parameter and region of interest are yet to be determined [4,6-12].The preponderance of studies on this subject has quantified the apparent diffusion coefficient (ADC) within regions of interest defined by abnormal tumour-related enhancement [6,9,11]. In vivo, the ADC is primarily determined by cell density [4,8,13,14]. As a result, changes in the ADC are sensitive to early alterations in tissue microstructure related to cell death; these changes include cell swelling and loss of membrane integrity associated with early necrosis as well as cell shrinkage due to apoptosis [11,15]. Indeed, it has been demonstrated that changes in the ADC within enhancing regions of interest can be used to identify the response to chemotherapy earlier than standard MRI [9]. Recent evidence, however, suggests the importance of non-enhancing, infiltrative tumour, as defined on fluid attenuation inversion recovery (FLAIR) images, with respect to tumour progression [16,17]. This non-enhancing component of tumour seems to be of particular relevance to patients treated with anti-angiogenesis agents [16,17]. Since the ADC is sensitive to variations in vasogenic oedema (increasing oedema tends to decrease cell density), in addition to the aforementioned direct effects on tumour cells, we hypothesise that the ADC would be an ideal parameter to characterise the effects of treatment within regions of interest defined by abnormal tumour-related FLAIR signals.Although there are few data in patients with brain tumours, there is some evidence that parameters of diffusion anisotropy derived from diffusion tensor imaging (DTI) may more accurately depict early changes in brain tissue microstructure than the ADC in central nervous system (CNS) diseases [18]. Fractional anisotropy (FA) is a measure of the degree of directional variation of the diffusion of water protons. Like the ADC, FA has been shown to correlate with cell density [7,18,19], but FA provides additional information regarding the integrity and alignment of parenchymal fibre tracts [20]. A recent study in patients with primary brain tumours demonstrated increasing FA across the study population within regions of interest defined by tumour-related contrast enhancement as early as 1 day after initiation of chemotherapy [12]. This same study failed to detect a significant change in the ADC at the same time point, raising the possibility that FA may be a more sensitive parameter to early treatment response.Although these preliminary results are promising, the significance of such changes with respect to patient survival has not been widely studied. In addition, there are very few data regarding the test–retest reproducibility of these parameters in patients with primary brain tumours, information which is crucial for understanding whether changes in these parameters can be used to guide therapy. In particular, an understanding of the magnitude of variability intrinsic to the method will be required to ascribe significance to changes in these parameters that occur after therapy in an individual patient.The goal of this study is to use the repeatability of ADC and FA derived from DTI to devise a method by which prognostic significance can be assigned to changes in these parameters that occur after therapy in patients with glioblastoma multiforme. In particular, we prospectively identified the following two null hypotheses:

• Patients with an increase in FA within regions of interest defined by tumour-related enhancement will not survive longer than those with no change or a decrease in FA.
• Patients with a change in ADC within regions of interest defined by an abnormal FLAIR signal will not survive longer than those with no change.

Although it may seem counterintuitive to evaluate the significance of any change in the ADC without respect for direction, there is evidence that both increasing and decreasing the ADC may reflect a clinically relevant treatment response [9,11].     

Diffusion-weighted MRI as a potential imaging biomarker reflecting the metastatic potential of upper urinary tract cancer

Objective:

To evaluate the role of diffusion-weighted MRI (DW-MRI) as an imaging biomarker for upper urinary tract cancer (UUTC) that has already metastasized or will metastasize soon.

Methods:

61 patients clinically diagnosed with UUTC were prospectively enrolled in this study. All the patients underwent MRI, including DW-MRI, prior to any interventions. Correlations between apparent diffusion coefficient (ADC) and other clinicopathological variables, including metastasis-free survival, were analysed.

Results:

Median follow-up period was 938 days. Of the 61 patients, 12 had any metastases at the initial diagnosis. 11 patients developed metastases during the follow-up period. These 23 patients were categorized as “Metastatic”. Of the remaining 38 patients, 35 with a follow-up period longer than 400 days were categorized as “Localized”. ADC was significantly lower in the Metastatic category than in the Localized (p = 0.0002) category. Multivariate analysis of pre-operative variables identified ADC (cut-off value, 1.08 × 10⁻³ mm² s⁻¹) and clinical T stage based on T₂ weighted MRI as an independent predictive factor of metastatic UUTC. 46 patients without any metastases during the initial diagnosis were stratified into a high-risk group (16 patients with low ADC and clinical T3–4) and a low-risk group (30 patients with high ADC or clinical Ta-2). The 3-year metastasis-free survivals were 45% and 93%, respectively.

Conclusion:

In the current study, UUTC with lower ADC value is more likely to have metastatic potential. Incorporating ADC with clinical T stage helps to differentiate metastatic UUTC at the initial diagnosis.

Advances in knowledge:

DW-MRI is a potential imaging biomarker reflecting metastatic propensity of UUTC.Upper urinary tract cancer (UUTC) is a potentially lethal disease. The prognosis remains poor even when standard care, radical nephroureterectomy (RNU) is performed, and almost one-third of the patients die within 5 years.^1–3 In the management of localized UUTC, adjuvant chemotherapy has no impact on survival, particularly owing to the impaired post-surgical renal function or comorbidity.⁴ However, neoadjuvant chemotherapy, which showed a survival benefit in bladder cancer,⁵ may have a similar benefit in UUTC.Neoadjuvant chemotherapy can be considered an option for locally advanced disease at diagnosis. Two nomograms are available for predicting locally advanced UUTC in the pre-operative setting: one includes tumour histological grade, architecture and location and the other includes histological grade and radiological clinical stage.^6,7 “Localized disease” at the initial diagnosis that will develop metastasis soon after RNU can also be a candidate for neoadjuvant chemotherapy. However, identifying these occult or developing metastases pre-operatively remains a challenge.Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that reveals physiological information by quantifying the diffusion of water molecules in tissues.⁸ The extent of water diffusion is quantified as the apparent diffusion coefficient (ADC). In 2009, a consensus meeting was held on the use of DW-MRI as a cancer imaging biomarker.⁹ An extraordinary opportunity for DW-MRI to evolve into a clinically valuable imaging tool was indicated. This imaging technique has been incorporated into general oncological imaging practices, including tissue characterization, monitoring the treatment response and predicting treatment outcome, in various cancers.^8,10–14Previous studies demonstrated the role of the ADC as a marker for the biological aggressiveness of UUTC by showing a correlation of the ADC with the histological grade and the Ki-67 labelling index.^14,15 Furthermore, the ADC was significantly associated with the cancer-specific survival after RNU.¹⁵ Therefore, we hypothesized that the ADC can be used as a marker to reflect the metastatic potential of UUTC, as has been reported in bladder cancer.¹⁶ The aim of this study is to show that the ADC can predict UUTC that has already metastasized or will metastasize soon. We first evaluated ADC values of the biologically metastatic UUTC and non-metastatic UUTC. Secondarily, we analysed the potential of the ADC to predict the development of metastasis.     

Femoral neck shaft angle width is associated with hip-fracture risk in males but not independently of femoral neck bone density

Objective:

To investigate the specificity of the neck shaft angle (NSA) to predict hip fracture in males.

Methods:

We consecutively studied 228 males without fracture and 38 with hip fracture. A further 49 males with spine fracture were studied to evaluate the specificity of NSA for hip-fracture prediction. Femoral neck (FN) bone mineral density (FN-BMD), NSA, hip axis length and FN diameter (FND) were measured in each subject by dual X-ray absorptiometry. Between-mean differences in the studied variables were tested by the unpaired t-test. The ability of NSA to predict hip fracture was tested by logistic regression.

Results:

Compared with controls, FN-BMD (p < 0.01) was significantly lower in both groups of males with fractures, whereas FND (p < 0.01) and NSA (p = 0.05) were higher only in the hip-fracture group. A significant inverse correlation (p < 0.01) was found between NSA and FN-BMD. By age-, height- and weight-corrected logistic regression, none of the tested geometric parameters, separately considered from FN-BMD, entered the best model to predict spine fracture, whereas NSA (p < 0.03) predicted hip fracture together with age (p < 0.001). When forced into the regression, FN-BMD (p < 0.001) became the only fracture predictor to enter the best model to predict both fracture types.

Conclusion:

NSA is associated with hip-fracture risk in males but is not independent of FN-BMD.

Advances in knowledge:

The lack of ability of NSA to predict hip fracture in males independent of FN-BMD should depend on its inverse correlation with FN-BMD by capturing, as the strongest fracture predictor, some of the effects of NSA on the hip fracture. Conversely, NSA in females does not correlate with FN-BMD but independently predicts hip fractures.Hip fracture is the worst osteoporotic fracture with regard to cost^1,2 and adverse consequences,^3,4 so its prevention by checking for the related fracture risk factors is an important goal. Although low bone mineral density (BMD) is generally recognized as the main risk factor for hip fracture,^5,6 there is growing evidence that other bone characteristics, such as proximal femur geometry (PFG) parameters, are implicated in determining the risk profile for hip fracture.^7,8 This evidence, however, mainly derives from studies carried out in females,^9–13 whereas contradictory results characterize studies carried out in males.^14–20 Authors'' opinions seem to vary widely about the ability of the neck shaft angle (NSA), one of the PFG factors, to predict osteoporotic hip fractures in males,^14–16,21 whereas its association with the risk of hip fracture in females^10,11,14,22 is generally accepted. Gender differences in the hip anatomy²³ have been put forward as a possible explanation for the different relationship of NSA with the hip-fracture risk between genders, whereas geographic and racial differences²⁴ among the examined male populations have been advocated as a possible cause of authors'' discrepancies on the relationship between NSA and the hip-fracture risk in males.This topic is therefore still under debate, and further studies are required to clarify the association of the NSA with hip-fracture risk in males. The authors of the current study contribute to this topic by studying the relationship between NSA and the hip fragility fracture in a sample of white Italian males.     

The challenge of segmental small bowel motility quantitation using MR enterography

Objective:

Analysis of “cine” MRI using segmental regions of interest (ROIs) has become increasingly popular for investigating bowel motility; however, variation in motility in healthy subjects both within and between scans remains poorly described.

Methods:

20 healthy individuals (mean age, 28 years; 14, males) underwent MR enterography to acquire dynamic motility scans in both breath hold (BH) and free breathing (FB) on 2 occasions. Motility data were quantitatively assessed by placing four ROIs per subject in different small bowel segments and applying two measures: (1) contractions per minute (CPM) and (2) Jacobian standard deviation (SD) motility score. Within-scan (between segment) variation was assessed using intraclass correlation (ICC), and repeatability was assessed using Bland–Altman limits of agreement (BA LoA).

Results:

Within-scan segmental variation: BH CPM and Jacobian SD metrics between the four segments demonstrated ICC R = 0.06, p = 0.100 and R = 0.20, p = 0.027 and in FB, the CPM and Jacobian SD metrics demonstrated ICC R = −0.26, p = 0.050 and R = 0.19, p = 0.030. Repeatability: BH CPM for matched segments ranged between 0 and 14 contractions with BA LoA of ±8.36 and Jacobian SD ranged between 0.09 and 0.51 with LoA of ±0.33. In FB data, CPM ranged between 0 and 10 contractions with BA LoA of ±7.25 and Jacobian SD ranged between 0.16 and 0.63 with LoA = ±0.28.

Conclusion:

The MRI-quantified small bowel motility in normal subjects demonstrates wide intersegmental variation and relatively poor repeatability over time.

Advances in knowledge:

This article presents baseline values for healthy individuals of within- and between-scan motility that are essential for understanding how this process changes in disease.Dynamic “cine” MRI acquired during MR enterography is increasingly utilized to assess bowel motility in a range of conditions, notably inflammatory bowel disease and enteric dysmotility syndromes.^1–4 Analysis of the data remains primarily subjective in clinical routine, but the ability to apply quantitative techniques makes this a potentially powerful methodology to explore gastrointestinal physiology in disease as well as an emerging application as a biomarker for drug efficacy.^5–7Despite the growing literature, a consensus has yet to be reached as to the best method of quantitatively analysing small bowel data and indeed a range of motility metrics are proposed.^2,3,8–12 The most commonly used metric is the change in luminal diameter at a fixed anatomical position through the time series. By tracking bowel diameter, a characteristic curve can be produced with the number of contractions expressed per minute (CPM) to give an intuitive and broadly accepted metric for small bowel motility (SBM).^{2–4,9,11,13–15} To date, several studies have reported a relationship between CPM and dysmotility in disease, either compared with a histopathological standard or “normal” reference bowel loops.^2–4,12 An array of additional metrics derived both from bowel diameter measures and more abstract processing techniques have further been implemented with varying degrees of effectiveness in disease and health.^{2,4,5,8,10,14,16}Although intuitively attractive, the robustness of assessing overall enteric motility using only an isolated loop of bowel has received relatively little attention to date irrespective of the precise metric applied. It is unclear how representative the selected bowel loops are of overall SBM and if normal motility intrinsically differs between bowel segments, for example, between the jejunum and ileum. Furthermore, the repeatability of single loop metrics, even in normal individuals, is not well described, knowledge of which is vital if segmental analysis is to be used to diagnose, guide treatment and monitor enteric pathology.The purpose of this study is to explore segmental variation in SBM in healthy volunteers measured using two commonly reported small bowel metrics [CPM and Jacobian standard deviation (SD)] looking at (1) within-scan motility variation between different segments and (2) between-scan variation (repeatability) across two time points.     

Correlation of the apparent diffusion coefficiency values on diffusion-weighted imaging with prognostic factors for breast cancer

Objective

The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of breast cancer with prognostic factors.

Methods

335 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) and ductal carcinoma in situ (DCIS) who underwent breast MRI with diffusion-weighted imaging were included in this study. ADC of breast cancer was calculated using two b factors (0 and 1000 s mm^–2). Mean ADCs of IDC NOS and DCIS were compared and evaluated. Among cases of IDC NOS, mean ADCs were compared with lymph node status, size and immunochemical prognostic factors using Student''s t-test. ADC was also correlated with histological grade using the Kruskal–Wallis test.

Results

Mean ADC of IDC NOS was significantly lower than that of DCIS (p<0.001). However, the mean ADC of histological grade of IDC NOS was not significantly different (p=0.564). Mean ADC of oestrogen receptor (ER)-positive or progesterone receptor (PR)-positive cancer was significantly lower than that of ER-negative or PR-negative cancer (p=0.003 vs p=0.032). Mean ADC of Ki-67 index-positive cancer was significantly lower than that of Ki-67 index-negative cancer (p=0.028). Mean ADC values of cancers with increased microvascular density (MVD) were significantly lower than those of cancer with no MVD increase (p=0.009). No correlations were observed between mean ADC value and human growth factor receptor 2 expression, tumour size and lymph node metastasis.

Conclusion

Low ADC value was correlated with positive expression of ER, PR, increased Ki-67 index, and increased MVD of breast cancer.Breast MRI is an established supplemental technique to mammography and ultrasonography for evaluation of suspicious breast lesions. Diffusion-weighted MRI (DWI) has recently been integrated into the standard breast MRI for discrimination of benign and malignant breast lesions obtained with dynamic contrast-enhanced MRI [1-13]. DWI is a non-invasive technique that represents the biological character of the mainly Brownian movement of protons in bulk water molecules in vivo. Apparent diffusion coefficient (ADC) values are quantified by measurement of mean diffusivity along three orthogonal directions, which are affected by cellularity of the tissue, fluid viscosity, membrane permeability and blood flow [7,9-11]. Microstructural characteristics, including water diffusion and blood microcirculations in capillary networks, were associated with ADC value. Decreased movement of molecules in highly cellular tissue showed correlation with a low ADC value [3,4]. Several studies of DWI of the breast have reported significantly lower ADC values in malignant tumours, compared with benign breast lesions and normal tissue [1-3,5-11,14]. Classic prognostic markers, including tumour size and grade, and lymph node status in patients with breast cancer, and molecular markers, including oestrogen receptor (ER), progesterone receptor (PR), Ki-67 index, human growth factor receptor 2 (HER2) protein and angiogenic molecular markers, have been reported [1,15,16]. Few studies have examined the correlation between ADC values and prognostic factors [1,8]. The purpose of this study is to compare ADC values of DWI of breast cancer with prognostic factors.     

Hepatic radiofrequency ablation: in vivo and ex vivo comparisons of 15-gauge (G) and 17-G internally cooled electrodes

Objective:

To compare the performance of the 15-G internally cooled electrode with that of the conventional 17-G internally cooled electrode.

Methods:

A total of 40 (20 for each electrode) and 20 ablation zones (10 for each electrode) were made in extracted bovine livers and in in vivo porcine livers, respectively. Technical parameters, three dimensions [long-axis diameter (Dl), vertical-axis diameter (Dv) and short-axis diameter (Ds)], volume and the circularity (Ds/Dl) of the ablation zone were compared.

Results:

The total delivered energy was higher in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (8.78 ± 1.06 vs 7.70 ± 0.98 kcal, p = 0.033; 11.20 ± 1.13 vs 8.49 ± 0.35 kcal, p = 0.001, respectively). The three dimensions of the ablation zone had a tendency to be larger in the 15-G group than in the 17-G group in both studies. The ablation volume was larger in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (29.61 ± 7.10 vs 23.86 ± 3.82 cm³, p = 0.015; 10.26 ± 2.28 vs 7.79 ± 1.68 cm³, p = 0.028, respectively). The circularity of ablation zone was not significantly different in both the studies.

Conclusion:

The size of ablation zone was larger in the 15-G internally cooled electrode than in the 17-G electrode in both ex vivo and in vivo studies.

Advances in knowledge:

Radiofrequency ablation of hepatic tumours using 15-G electrode is useful to create larger ablation zones.Radiofrequency ablation (RFA) is the most widely used local ablation technique for the management of primary and metastatic liver tumours. However, previous studies have reported that RFA showed a relatively higher local tumour progression rate than did hepatic resection.^1,2 One of the most important factors affecting local tumour progression was insufficient tumour-free ablation margin of hepatic parenchyma around the tumour margin.^3–6Several strategies have been developed to obtain sufficient ablation margin. In the aspect of RFA techniques, overlapping technique and combined treatment with transcatheter arterial chemoembolization can be used.^7–9 Another strategy is to use switching monopolar, bipolar or multipolar modes to deliver radiofrequency (RF) energy more efficiently.^10,11 Sufficient ablation margin can also be achieved by more efficient electrodes: internally cooled electrode increases the size of ablation zone by preventing charring around the electrode tip.^12,13 Perfusion electrodes can also enlarge the ablation zone by increasing electrical conductance and thermal conductivity.^14–16The diameter of an electrode is also known to be associated with the size of the ablation zone. Theoretically, as the diameter of an electrode becomes larger, the contact surface of the electrode with the surrounding tissue becomes bigger, thereby increasing the active electric field.^17,18 As a result, an electrode with a larger diameter is likely to create a larger ablation zone. In a previous study, Goldberg et al¹⁷ reported that the extent of coagulation necrosis by RFA increases as the diameter of an electrode increases through an in vivo experimental study. However, this study was performed with an electrode without an internal cooling system. Recently, a clinical study comparing therapeutic efficacy and safety between 15-G and 17-G internally cooled electrodes of RFA for hepatocellular carcinoma was published.¹⁹ According to that study, the 15-G internally cooled electrode created a larger ablation volume than did the 17-G electrode. However, the study was limited by selection bias owing to the retrospective study design. In addition, the ablation protocol was not exactly the same between the two groups. Therefore, the issue whether an internally cooled electrode with a larger diameter creates a larger ablation volume should be verified with ex vivo and in vivo experimental studies.The purpose of this experimental study was to compare the performance of the 15-G internally cooled RF electrode with that of the conventional 17-G electrode in both ex vivo and in vivo studies.     

Diffusion-weighted imaging vs STIR turbo SE imaging: capability for quantitative differentiation of small-cell lung cancer from non-small-cell lung cancer

Objective:

To compare the capability of differentiation of small-cell lung cancer (SCLC) from non-SCLC (NSCLC) between diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR) turbo spin-echo imaging.

Methods:

The institutional review board of Kobe University Hospital, Kobe, Japan, approved this study, and written informed consent was obtained from each patient. 49 patients with NSCLC (30 males and 19 females; mean age, 66.8 years) and 7 patients with SCLC (5 males and 2 females; mean age, 68.6 years) enrolled and underwent DWI and STIR. To quantitatively differentiate SCLC from NSCLC, apparent diffusion coefficient (ADC) values on DWI and contrast ratios (CRs) between cancer and muscle on STIR were evaluated. ADC values and CRs were then compared between the two cell types by Mann–Whitney''s U-tests, and the diagnostic performances were compared by McNemar''s test.

Results:

There were significant differences of mean ADC values (p < 0.001) and mean CRs (p = 0.003). With adopted threshold values, the specificity (85.7%) and accuracy (85.7%) of DWI were higher than those of STIR (specificity, 63.3%; p = 0.001 and accuracy, 66.1%; p = 0.001). In addition, the accuracy of combination of both indexes (94.6%; p = 0.04) could significantly improve as compared with DWI alone.

Conclusion:

DWI is more useful for the differentiation of SCLC from NSCLC than STIR, and their combination can significantly improve the accuracy in this setting.

Advances in knowledge:

Pulmonary MRI, including DWI and STIR, had a potential of the suggestion of the possibility as SCLC.Lung cancer is the most common cause of cancer-related death among both males and females worldwide.¹ Lung cancers are divided into non-small-cell cancer (NSCLC) and small-cell lung cancer (SCLC), and the differentiation between SCLC and NSCLC is important in clinical practice because their therapeutic strategies, clinical course and prognoses are different.² In general, SCLC is usually determined with extensive hilar and mediastinal lymphadenopathy,³ and these cancers are mainly treated by chemotherapy or chemoradiotherapy.^2,4On the other hand, 5–10% of patients with SCLC were diagnosed as having solitary pulmonary nodules.^5,6 In this situation, the assessments of distant metastases before treatment play an important role in deciding the treatment. At present, although there are some different reports for patients with NSCLC regarding the assessment of distant metastases before surgery,^7–9 it is important to assess the distant metastases of these patients with SCLC because SCLC is known for its rapid doubling time, high growth fraction and early development of metastatic disease.^10–12 If patients with SCLC are diagnosed at Stage I or possibly Stage II, clinicians consider their treatment as surgery and/or neoadjuvant chemotherapy.^13–15 Therefore, the differentiation between SCLC and NSCLC and the suggestion of the possibility of SCLC may be important in routine clinical practice. However, the differentiation of SCLC from NSCLC is difficult on CT and positron emission tomography (PET) or PET/CT,^5,6,16 and fiberoptic bronchoscopy and percutaneous biopsy are recommended, although their diagnostic sensitivities range from 67% to 100%.^17–19Recently, the image quality and diagnostic capability of chest MRI has improved because of the advancement of MR systems and sequences, and short tau inversion recovery (STIR) turbo spin-echo (SE) imaging and diffusion-weighted imaging (DWI) have been reported as useful in differentiating malignant nodules and lymph nodes from benign ones in several articles.^20–25 Meanwhile, the utilities of chest MRI, including STIR and DWI, have been reported,²⁶ and, in addition, meta-analysis report for pulmonary nodules by means of DWI have been published.²⁷ However, to the best of our knowledge, there have been only reports of chest DWI regarding the differentiation between SCLC and NSCLC,²² but no major studies have reported a direct comparison of the use of DWI and STIR in chest MRI for the assessment of differentiation between SCLC and NSCLC. We hypothesized that both DWI and STIR were useful MR sequences for differentiation of SCLC from NSCLC and their combination might improve the differentiation capabilities. The aim of this study was to evaluate the diagnostic performances of DWI and STIR for differentiating between SCLC and NSCLC.     

Radiographers' professional knowledge regarding parameters and safety issues in plain radiography: a questionnaire survey

Objective:

To review the knowledge of radiographers and examine the possible sociodemographic and situational contributors to this knowledge.

Methods:

A questionnaire survey was devised and distributed to a cohort of 120 radiographers. Each questionnaire contained two sections. In the first section, background data, including sex, age, highest academic level, grade point average (GPA), length of time from graduation, work experience as a radiographer and the status of previous refresher course(s), were collected. The second section contained 17 multiple-choice questions concerning radiographic imaging parameters and safety issues.

Results:

The response rate was 63.8%. In univariate analytic model, higher academic degree (p < 0.001), higher GPA (r² = 0.11; p = 0.001), academic workplace (p = 0.04) and taking previous refresher course(s) (p = 0.01) were significantly associated with higher knowledge score. In multivariate analytic model, however, higher academic degree (B = 1.62; p = 0.01), higher GPA (B = 0.50; p = 0.01) and taking previous refresher course(s) (B = −1.26; p = 0.03) were independently associated with higher level of knowledge. Age, sex, length of time from graduation and work experience were not associated with the respondents'' knowledge score.

Conclusion:

Academic background is a robust indicator of a radiographer''s professional knowledge. Refresher courses and regular knowledge assessments are highly recommended.

Advances in knowledge:

This is the first study in the literature that examines professional knowledge of radiographers in terms of technical and safety issues in plain radiography. Academic degree, GPA and refresher courses are independent predictors of this knowledge. Regular radiographer professional knowledge checks may be recommended.The Joint Commission on Accreditation of Healthcare Organizations mandates “processes that are designed to ensure that the competency of all staff members is assessed, maintained, demonstrated and improved on an ongoing basis.” Tests with practical questions that reflect the knowledge required to perform daily examinations have been proposed as effective tools to attain this purpose. The results enable us to take on existing blemishes and improve the competency.¹Medical imaging, as a field with growing complexity and increasing impact on diagnosis, plans of management and patient health status,² is a good example of raised requirements for competency.^3–8Knowledge assessment may be useful for detecting possible weaknesses in an organization and spotlighting existing educational flaws and shortcomings.⁹ According to some reports, knowledge assessment takes priority over checking competency,^7,10 particularly in professions that are completely mediated by technology.¹¹In addition, although clinical education is the mainstay for developing skills, it has been shown that the combination of practical and theoretical education would lead to a significantly better outcome in the field of teaching. This integrated approach of using both knowledge and practice in education enables the trainee to work more competently and be prepared to take responsibility in his/her future career.¹²Although radiography using film for imaging the internal organs of the body has been introduced for over a century,¹³ it is still among the most widespread and useful imaging modalities all over the world. Radiographers are generally in charge of radiological equipment, imaging examination and frequently nursing care.^7,14,15Incompetent radiographers could render radiographic examinations suboptimal. A poor radiographic technique, in turn, may lead to unnecessary exposures to X-radiation, poor image quality, repeated views and examinations, patient discomfort or further injury because of poor positioning and the possibility of a missed diagnosis or misdiagnosis.¹⁶Furthermore, a rapid shift from conventional to fully digitized radiology departments, along with rapidly evolving changes in healthcare administration¹⁷ entails knowledgeable, up-to-date radiographers who utilize the technology.¹⁸Except for very limited number of studies that have described radiographers'' self-reported competency^7,16 and the level of awareness pertaining to the protection against radiation,^19,20 to the best of our knowledge, there is no study in the literature regarding radiographers'' level of knowledge with a dedicated focus on technical parameters and safety in plain radiography.This study sets out to examine knowledge amongst a cohort of radiographers and to investigate possible association of some sociodemographic and situational factors with the level of this knowledge.     

Medial temporal lobe atrophy in Alzheimer's disease/mild cognitive impairment with depression

Objective:

Depression is common in patients with Alzheimer''s disease (AD) and mild cognitive impairment (MCI). Patients with depression have an earlier onset and rapid progression of cognitive decline. Medial temporal lobe atrophy (MTA) is common in AD and MCI, and some degree of atrophy is found in almost all patients. In the present study, an attempt was made to know if MTA is more common in patients with AD/MCI with depression than those without it.

Methods:

Patients reporting to the outpatient department of a neurology centre of a tertiary care hospital were recruited for the present study. After initial general physical and neurological examination, they were evaluated using National Institute of Neurological and Communicative Disorders and Stroke and Related Disorders Association criteria for diagnosis of AD. Clinical Dementia rating scale was used for the diagnosis of MCI. Cornell scale for depression in dementia (CSDD) was used.

Results:

We found 20 cases with depression as per CSDD out of a sample of 37 patients (male:female = 30:7). There were 26 patients with AD and 11 with MCI. The mean age of all patients was 72.33 ± 6.45 years. The mean mini mental status examination score was 19.00 ± 6.73. The mean time since diagnosis was 4.19 ± 3.26 years. The mean Scheltens visual rating scale score for right MTA was 2.08 ± 0.95 and was 2.05 ± 0.94 for the left. Both scores did not differ statistically when analyzed using paired t-test (p > 0.05). However, difference in those with depression (2.36 ± 0.95) from those without depression (1.60 ± 0.74) was significant (p < 0.05).

Conclusion:

MTA scores were higher in those with AD/MCI with depression than those without it.Depression¹ is common in patients with Alzheimer''s disease (AD) and mild cognitive impairment (MCI). Relationship between depression and cognitive decline is a complex one, and depression is both an aetiological risk factor² and comorbidity for dementia.³ Incidence and prevalence of depressive symptoms in MCI range from 15% in population-based studies to 44% in hospital-based studies.⁴ Likewise, up to two-thirds of patients with AD have been reported to have depression.⁵ Because in many studies, depression has been seen to be an early manifestation of AD, it has been suggested that it may represent a continuum⁴ from depression to MCI to AD (late-life depression → MCI → AD). Two recent meta-analyses have found that a history of depression approximately doubles an individual''s risk for subsequent dementia in general and AD in particular.⁶ Depression is known to be neurotoxic to medial temporal lobe structures and can contribute to their atrophy.^7–9 Atrophy is more so, when depression is severe or recurrent⁷ and medial temporal lobe atrophy (MTA) has a temporal association with depression.⁹ Continued treatment of depression has been shown to protect the hippocampus from the ill effects of depression.¹⁰ Although volumetric method could be a preferred mode of measuring the hippocampal volume in AD, qualitative rating of MTA is a good alternative.¹¹ Visual rating of the hippocampal volume^12–14 can be carried out using Scheltens et al¹⁵ rating scale that is based on the width of the choroid fissure, the width of the temporal horn and the height of hippocampal formation and is a quantitative scale.     

Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre)

Objective:

Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre).

Methods:

Real-time phase-contrast flow MRI at 3 T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s).

Results:

Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p < 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1–2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization.

Conclusion:

Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution.

Advances in knowledge:

Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised.The Valsalva manoeuvre attempts to increase the intrathoracic pressure by a forceful expiration against a closed glottis, typically for a few seconds. The resulting haemodynamic response is characterized by a sinusoidal waveform of arterial pressure and stroke volume. The pattern is caused by an acute increase in intrathoracic pressure (Phase 1), a decreased stroke volume secondary to decreased venous return (Phase 2), an acute decrease of intrathoracic pressure during early recovery (Phase 3) and a subsequent increase in stroke volume accompanied by a reflex bradycardia (Phase 4).¹Current applications of the Valsalva manoeuvre focus on specific cardiovascular questions.² For example, a clinical indication in combination with Doppler echocardiography to distinguish normal from pseudonormal mitral inflow in ventricular diastolic dysfunction.³ In general, however, the clinical relevance of the Valsalva manoeuvre suffers from difficulties in the non-invasive quantification of blood flow dynamics and the inability to assess haemodynamic functions simultaneously in the superior vena cava (SVC) and with respect to left-ventricular outflow.⁴ Moreover, because the manoeuvre is inevitably associated with a forced and increased breathing frequency during strain release, echocardiographic studies may be compromised by the lack of an appropriate acoustic window.On the other hand, MRI techniques have emerged as a new diagnostic standard for simultaneous evaluation of left-ventricular and right-ventricular function.⁵ In particular, velocity-encoded phase-contrast flow MRI^6–8 allows for a non-invasive quantification of blood flow in all major heart vessels.^9,10 So far, however, a fundamental limitation of current cine MRI techniques is their dependency on the electrocardiogram (ECG), either for triggering or retrospective sorting of data acquisitions, and on measurements that cover multiple heartbeats (with or without breath holding). ECG-synchronized cine MRI is therefore not applicable for studying the immediate haemodynamic alterations associated with the Valsalva manoeuvre.This problem may be overcome by real-time MRI as previously demonstrated using different technical approaches.^11–15 Here, we present a new study of the cardiovascular responses to the Valsalva manoeuvre, which exploits recent progress in real-time MRI yielding improved spatiotemporal resolution and image quality.^16,17 Respective extensions allow for dynamic measurements of cardiovascular function^18,19 and blood flow^20,21 in real time. In particular, the present study applies a real-time phase-contrast MRI technique for measuring through-plane flow at a temporal resolution of 40 ms and a spatial resolution of 1.33 mm.²¹ It offers a simultaneous assessment of flow in the ascending aorta (AA) and SVC. Quantification of blood flow is achieved for successive individual heartbeats and therefore provides access to the immediate cardiac and haemodynamic responses to medication, exercise or stress as, for example, imposed by changes of intrathoracic pressure. In this first study of healthy subjects, we evaluated the physiological responses to the Valsalva manoeuvre in more detail than possible by Doppler echocardiography.     

Assessment of early treatment response after CT-guided radiofrequency ablation of unresectable lung tumours by diffusion-weighted MRI: a pilot study

The aim of this study was to evaluate prospectively the early treatment response after CT-guided radiofrequency ablation (RFA) of unresectable lung tumours by MRI including diffusion-weighted imaging (DWI). The study protocol was approved by the ethics committee of our hospital and signed consent was obtained from each patient. We studied 17 patients with 20 lung lesions (13 men and 4 women; mean age, 69±9.8 years; mean tumour size, 20.8±9.0 mm) who underwent RFA using a LeVeen electrode between November 2006 and January 2008. MRI was performed on a 1.5T unit before and 3 days after ablation. We compared changes in the apparent diffusion coefficient (ADC) on DWI and response evaluation based on subsequent follow-up CT. 14 of the 20 treatment sessions showed no local progression on follow-up CT, whereas 6 treatment sessions showed local progression (range, 3–17 months; mean, 6 months). For the no-progression group, the ADC pre- and post-RFA were 1.15±0.31 × 10⁻³ mm² s⁻¹ and 1.49±0.24 × 10⁻³ mm² s⁻¹, respectively, while the respective ADC values for those that showed local progression were 1.05±0.27 × 10⁻³ mm² s⁻¹ and 1.24±0.20 × 10⁻³ mm² s⁻¹. The ADC of the ablated lesion was significantly higher than before the procedure (p<0.05). There was a significant difference in the ADC post-RFA between no-progression and local progression groups (p<0.05). Our prospective pilot study showed that the ADC without local progression was significantly higher than with local progression after RFA, suggesting that the ADC can predict the response to RFA for lung tumours.After the first report in 2000 [1], lung radiofrequency ablation (RFA) is now considered effective in the treatment of lung cancer, which is traditionally considered unresectable owing to compromised pulmonary function or advanced age. In general, complications associated with lung RFA are minimal, and favourable local control has been reported in a number of studies of tumours with a diameter of 30 mm or less [1–5]. However, only a limited number of studies have been published regarding the treatment outcome after lung RFA [6–10]. In this process, a layer of normal lung tissue surrounding the tumour is also ablated as a safety margin. Inevitably, the ablated lesion depicted on a CT scan immediately after the procedure is larger than the original tumour mass. However, this region of increased density shrinks with time, but follow-up CT may still show the ablated lesion being as big as, or larger than, the tumour size before the procedure [6, 7]. Thus, radiologists sometimes encounter difficulty in distinguishing scarred tissue from a tumour residue/local progression when the size of the lesion remains the same. Accurate assessment of RFA outcome would have important consequences, as recurrent tumours can be treated again if detected at an early stage. Different modalities of early-stage follow-up examination, such as contrast-enhanced CT [8] and fluorodeoxyglucose positron emission tomography (FDG–PET), have been of great interest and their usefulness has been reported by several groups [9, 10]. Another approach — MR diffusion-weighted imaging (DWI) — which is based on the measurement of motion of water molecules, has also been reported as a non-invasive evaluation modality [11–19]. In this method, the apparent diffusion coefficient (ADC) represents the water content and distribution, the cellular density and the cell membrane integrity, suggesting the potential usefulness of an ADC map for estimating tumour viability. Indeed, DWI has been successfully used to assess the efficacy of radiotherapy [11, 12], chemotherapy [13–15] and transcatheter arterial embolisation [16, 17]. To our knowledge, only two studies have reported the use of DWI to evaluate the therapeutic outcome of RFA [18, 19]. A previous study reported that the ADC value of an ablated rabbit tumour model (VX2 tumour) was significantly higher than that of untreated tumours, and that FDG uptake on micro-PET for small animals with ablated tumours was significantly lower than for untreated tumours. These results indicate that DWI at 2 days and FDG–PET at 3 days after RFA are both potentially feasible modalities for monitoring the early effects of the procedure [19]. In this study, we calculated the ADC in tumour lesions before and after clinical lung RFA and examined the usefulness of DWI in the early detection of tumour response to RFA.     

A planning target volume margin formula for hypofractionated intracranial stereotactic radiotherapy under cone beam CT image guidance with a six-degrees-of-freedom robotic couch and a mouthpiece-assisted mask system: a preliminary study

Objective:

A planning target volume (PTV) margin formula for hypofractionated intracranial stereotactic radiotherapy (SRT) has been proposed under cone beam CT (CBCT) image guidance with a six-degrees-of-freedom (6-DOF) robotic couch.

Methods:

CBCT-based registration using a 6-DOF couch reportedly led to negligibly small systematic positioning errors, suggesting that each in-treatment positioning error during the treatment courses for the patients employing this combination was predominantly caused by a random gaussian process. Under this assumption, an anisotropic PTV margin for each axis was formulated based on a gaussian distribution model. 19 patients with intracranial lesions who underwent additional post-treatment CBCT were consecutively selected, to whom stereotactic hypofractionated radiotherapy was delivered by a linear accelerator equipped with a CBCT imager, a 6-DOF couch and a mouthpiece-assisted mask system. Time-averaged patient-positioning errors during treatment were estimated by comparing the post-treatment CBCT with the reference planning CT images.

Results:

It was suggested that each histogram of the in-treatment positioning error in each axis would approach each single gaussian distribution with a mean of zero. The calculated PTV margins in the x, y and z directions were 0.97, 1.30 and 0.88 mm, respectively.

Conclusion:

The empirical isotropic PTV margin of 2 mm used in our facility for intracranial SRT was consistent with the margin calculated by the proposed gaussian model.

Advances in knowledge:

We have proposed a PTV margin formula for hypofractionated intracranial SRT under CBCT image guidance with a 6-DOF robotic couch.Frameless radiotherapy for treating intracranial lesions has been widely adopted under the guidance of on-board cone beam CT (CBCT) and a mask system with a six-degrees-of-freedom (6-DOF) robotic couch^1–3 or a semi-robotic couch including manual angle adjustments.⁴ Reported maximum registration errors along any Cartesian co-ordinate axis were 0.5 mm for a phantom;¹ and 1.0 or 3.2 mm (mask dependent),² 2.0 ³ and 1.2 mm⁴ for patients. The mean ± standard deviation (SD) along any Cartesian co-ordinate axis was 0.07 ± 0.17 mm for a phantom based on 12 plans and 5 repeated CBCT acquisitions,¹ 0.2 ± 0.4 mm for 10 patients with 6 fractions³ and 0.4 ± 0.3 mm for a phantom and 0.5 ± 0.3 mm for patients including manual couch angle adjustments.⁴ Meyer et al¹ stated that there was no systematic error because they observed a small mean error for their phantom study.Margins between clinical target volumes (CTVs) and planning target volumes (PTVs) are often calculated using a formula proposed by van Herk et al.^5,6 This formula employed two independent statistical models including a patient-to-patient variation model that gives a mean preparation error in all fractions for each patient, and a random error model during treatment delivery owing to random tumour movement. A patient population coverage probability of 90% in a facility was calculated by the patient-to-patient variation model, and the random error model was used to add further margins by increasing penumbra widths. Our intracranial stereotactic radiotherapy (SRT) utilizes an Elekta Synergy® (Elekta AB, Stockholm, Sweden) linear accelerator (linac) equipped with a CBCT imager, XVI and a 6-DOF robotic couch, HexaPOD™ (Elekta AB), which are identical to the system that Meyer et al¹ described. Consequently, our study can be based on the small mean preparation error reported by Meyer et al, and the above margin model may not be applicable. In addition, the previous margin model assumed that the tumour was spherical, and the margin was defined in the radial direction of the spherical co-ordinate system. For example, Guckenberger et al² calculated the PTV margin in the radial direction using registration results for 47 patients with various treatment sites and fixation means, leading to a PTV margin of 1.7 mm that achieved 90% population coverage. Meanwhile, a more accurate margin formula in the Cartesian co-ordinate system that complies with patient couch movements was proposed, in which the margins were anisotropically defined along the x, y and z directions.⁷The purpose of this study was to propose a PTV margin formula as per the Cartesian co-ordinate system for hypofractionated intracranial SRT under CBCT image guidance with a 6-DOF robotic couch.