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.     

3-T diffusion tensor imaging (DTI) of normal uterus in young and middle-aged females during the menstrual cycle: evaluation of the cyclic changes of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values

Objective:

To evaluate cyclic changes of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of normal uterus in different age groups during the menstrual cycle, and the correlation with serum female hormone levels.

Methods:

29 normal volunteers accepted diffusion tensor imaging of the uterus on menstrual phase (MP), follicular phase (FP), ovulatory phase (OP) and luteal phase. FA and ADC values of different uterine layers on midsagittal images were measured. Differences between two age groups during the menstrual cycle were evaluated using liner mixed models and one-way analysis of variance. Pearson correlation analysis compared variation of FA and ADC values with serum female hormone levels measured in MP.

Results:

During menstrual cycle, endometrial FA values declined, whereas ADC values increased with significant differences (p < 0.05). Serum oestradiol (E) levels correlated moderately with variations of FA values between MP-FP (p = 0.045; r = 0.389) and MP-OP (p = 0.008; r = 0.511). FA and ADC values of junctional zones showed no significant difference (p > 0.05) as well as FA values of myometrium (p = 0.0961), while ADC values of myometrium showed significant increase from menstrual phase to luteal phase (p < 0.05). FA and ADC values of uterine three zonal structures showed significant differences (p < 0.05) at each phase during the menstrual cycle. No significant difference of FA and ADC values was found between age groups (p > 0.05).

Conclusion:

Dynamic changes of uterine FA and ADC values were observed during menstrual cycle. Variation of FA values between MP-FP, MP-OP correlated moderately with serum E levels.

Advances in knowledge:

No publications on the relationship between FA and ADC values and the female hormone levels were found; our study prospectively investigated the cyclic changes of FA and ADC values of the normal uterus and the correlation with the basic serum female hormone levels in MP.Diffusion tensor imaging (DTI) is a well-established technique, which has been widely used in variable neurological diseases^1–4 and other parts of the body, such as the musculoskeletal system,^5,6 prostate^7,8 and kidney.^9,10In recent years, limited publications of its application in the female pelvis have been emerging. Current published studies include ex vivo and in vivo studies.^11–16 In 2006, three-dimensional fibre architecture of the normal human uterus based on DTI has been ex vivo evaluated in five samples by Weiss et al.¹¹ Toba et al¹² ex vivo study showed that DTI might be a useful tool for the diagnosis of myometrial invasion of uterine endometrial cancer. However, fractional anisotropy (FA) value of a normal uterus has not been thoroughly investigated yet. What is more there is no known publication, to the best of our knowledge, found on the relationship between FA value and female menstrual cycle. It would be ambiguous to use this MR parameter to evaluate malignancy situations without knowing the possible differences in various uterine structures, including endometrium, myometrium and junctional zone. In 2012, Fiocchi et al¹³ investigated the feasibility of depicting fibre architecture of the human uterus in vivo using 3-T MR-DTI based on 30 volunteers in different menstrual phases (MPs). In 2013, Fujimoto et al¹⁴ compared the DTI parameters in the different uterine layers of nine subjects in vivo, but limited their study group to the luteal phase (LP) only. A more comprehensive study based on 11 normal young females was reported by Kido et al;¹⁵ however, only apparent diffusion coefficient (ADC) value changes were evaluated during three phases of menstrual cycle. To the best of our knowledge, there are no published data focused on the cyclic changes of FA value in a normal uterus during four phases of menstrual cycle with a larger study cohort. Moreover, as it has been learned from MRI studies, anatomical and physiological characteristics of uterine structures, such as the endometrium and junctional zone, are heavily related to female hormone levels.^17–22 Nevertheless, no publications on the relationships between FA or ADC values and the hormone level were found.So, the aim of our study was to prospectively investigate the cyclic changes of FA and ADC values of the normal uterus in a larger population divided into different age groups during the four phases of the menstrual cycle, and the correlation with the basic serum hormone levels in MP.     

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.     

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.     

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.     

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.     

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

Objective:

To determine the prognostic value of pre-treatment apparent diffusion coefficient (ADC) of colorectal liver metastases in predicting disease response, progression-free survival (PFS) and overall survival (OS).

Methods:

We retrospectively reviewed 102 patients who underwent pre-treatment diffusion-weighted MRI using a breath-hold (b=0, 150, 500) or a free-breathing (b=0, 50, 100, 250, 500, 750) technique. The mean ADC (b=0–500) and mean flow-insensitive ADC (ADC_high) values (breath-hold: b=150 and 500; free-breathing: b=100 and 500) of up to three hepatic lesions were evaluated in each patient. Clinical and laboratory parameters were recorded. Tumour response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 12 weeks after treatment. Associations between tumour response, ADC values and clinical/laboratory parameters were examined by one-way analysis of variance. The relationship of ADC with PFS and OS was determined by Kaplan–Meier analysis.

Results:

62 patients responded to chemotherapy at 12 weeks. The pre-treatment mean ADC and mean ADC_high were higher in the non-responding group than in the responding group (1.55 vs 1.36, p=0.033; 1.40 vs 1.16, p=0.024). However, the PFS and OS of the two groups of patients stratified by the median of mean ADC values or threshold derived by receiver operating characteristic analysis were not statistically significant. By multivariate Cox regression analysis, patients with ≤2 metastases and response to chemotherapy showed better PFS; white cell count ≤10 and surgical treatment were associated with better OS.

Conclusion:

Colorectal liver metastasis with higher pre-treatment mean ADC and mean ADC_high was associated with poorer response to chemotherapy. However, ADC and ADC_high values did not predict the patient outcome in this study cohort.

Advances in knowledge:

High mean ADC values of colorectal liver metastases on pre-treatment diffusion-weighted MRI is associated with poorer response to chemotherapy.Liver metastasis from colorectal cancer is common and is associated with poor survival. It has been shown that liver metastectomy [1], radiofrequency ablation [2] and good response to chemotherapy confer a favourable long-term outcome [3]. Given the impact of adverse effects of current treatments on quality of life, knowledge on the likelihood to respond to chemotherapy, progression-free survival (PFS) and overall survival (OS) will also facilitate clinical decision making on how aggressively to pursue the various therapeutic options.There are several pre-treatment clinical factors that have been shown to affect the outcome in metastatic colorectal cancer [4]. Negative clinical predictors of outcome include platelets (plt) >400×10⁹ l⁻¹, alkaline phosphatase (ALP) >300 units per litre, white blood cell count (WCC) >10×10⁹ l⁻¹, and haemoglobin (Hb) <11×10⁹ l⁻¹. The presence of lung or lymph node metastases and the primary site being at the rectum are associated with better outlook. However, there is currently no imaging-derived prognostic index that is linked to treatment outcomes. An MRI prognostic feature is attractive because it can be derived non-invasively and may also be applied for response monitoring.The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DW-MRI), provides information on the microscopic movement of water molecules [5–7]. In neoplasms, ADC informs on cell membrane integrity, cellular density, extracellular space tortuosity and microstructural organisation [8,9]. Solid tumours usually return lower ADC values than their tissue of origin. In brain tumours, a pre-treatment ADC value has been shown to predict tumour response [10] and disease survival [11]. Although studies have shown that a high pre-treatment ADC value of colorectal liver metastases predicts poor response to chemotherapy [12,13], the relationship of pre-treatment ADC value and the patient clinical outcome has not been examined in abdominal malignancies.The aim of this study was to determine whether pre-treatment ADC of colorectal liver metastases is of prognostic value in predicting the patient outcome in terms of disease response, PFS and OS.     

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.     

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.     

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.     

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.     

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.     

Walking on thin ice! Identifying methamphetamine “drug mules” on digital plain radiography

Objective:

The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of identifying methamphetamine (MA) internal payloads in “drug mules” by plain abdominal digital radiography (DR).

Methods:

The study consisted of 35 individuals suspected of internal MA drug containers. A total of 59 supine digital radiographs were collected. An overall calculation regarding the diagnostic accuracy for all “drug mules” and a specific evaluation concerning the radiological appearance of drug packs as well as the rate of clearance and complications in correlation with the reader''s experience were performed. The gold standard was the presence of secured drug packs in the faeces.

Results:

There were 16 true-positive “drug mules” identified. DR of all drug carriers for Group 1 (forensic imaging experienced readers, n = 2) exhibited a sensitivity of 100%, a mean specificity of 76.3%, positive predictive value (PPV) of 78.5%, negative predictive value (NPV) of 100% and a mean accuracy 87.2%. Group 2 (inexperienced readers, n = 3) showed a lower sensitivity (93.7%), a mean specificity of 86%, a PPV of 86.5%, an NPV of 94.1% and a mean accuracy of 89.5%. The interrater agreement within Group 1 was 0.72 and within Group 2 averaged to 0.79, indicating a fair to very good agreement.

Conclusion:

DR is a valuable screening tool in cases of MA body packers with huge internal payloads being associated with a high diagnostic insecurity. Diagnostic insecurity on plain films may be overcome by low-dose CT as a cross-sectional imaging modality and addressed by improved radiological education in reporting drug carriers on imaging.

Advances in knowledge:

Diagnostic signs (double-condom and halo signs) on digital plain radiography are specific in MA “drug mules”, although DR is associated with high diagnostic insecurity and underreports the total internal payload.For the past decade, significant worldwide manufacturing of amphetamine-type stimulants has been reported to the United Nations Office on Drugs and Crime, Vienna, Austria, with a predominance of methamphetamine (MA) and its derivatives, which are also known as “syabu” or “ice”, throughout East and South East Asia.¹ In this region, the use of this synthetic drug is more prevalent than that of cocaine or heroin, which are more common in relatively developed areas, such as Europe and the USA.² During the course of this development, an increase in the number of drug carriers being intercepted by law enforcement at the borders of Malaysia has been observed. Drug carriers or “drug mules” are generally referred to as a human harbouring internal illicit drug packet(s). Internal body concealment of illegal drugs is one of the methods used to smuggle this illicit drug across the border.^3,4 “Drug mules” are generally known as body packers.^5,6 However, for correct terminology, one should differentiate between the terms body packer, body pusher and body stuffer. A body packer swallows a large amount of specially prepared drug packets to smuggle the packets in their gastrointestinal tract across a national border.^5,6 A body pusher hides a few containers in easily accessible body cavities, such as the rectum or vagina. Body stuffers, including traffickers and users, ingest intentionally small amounts of loosely wrapped drug pellets (typically initially hidden in the mouth), usually immediately before an unexpected encounter with law enforcement.^5–10The generally accepted radiological examination is a plain abdominal radiograph in the supine projection.^4–6 This technique is widely available at a low cost and is a simple method of detecting drug-filled packets within the alimentary tract. Radiation exposure to the patient is relatively moderate. In the literature, the detection rate for drug-filled packets is highly variable, and sensitivities from 58.3% to 90% have been reported.^4,5,11 Hence, plain abdominal radiography is a flawed screening method for identifying “drug mules”. Examining the bowel for foreign bodies, such as drug containers with variable sizes and radiodensities, is problematic, even for an experienced radiologist because the drug-filled packets may have an appearance similar to that of stool and gas and may be superimposed. Specific appearances described in the literature, such as the “double-condom”, “halo” and “rosette” signs, may be diagnostic for drug packages but are not necessarily so.^{4–6,11–13} Other modalities employed worldwide for the identification of body packers include CT, ultrasound, MRI and low-dose linear slit digital radiography (LSDR or LODOX®; Lodox Systems, Johannesburg, South Africa).^4,5,14–18Recent research has mainly concentrated on cocaine and heroin drug trafficking, which occurs predominantly in Western countries.^{3,4,6,7,11,14,19} There is little research on the accuracy of plain abdominal radiography in MA drug carriers, although there has been a significant increase of MA in Asia, accompanied by draconian legal measures in cases of drug trafficking.^1,2 The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of plain abdominal digital radiography (DRL) for identifying the internal payloads of MA in “drug mules”.     

Grading of small hepatocellular carcinomas (≤2 cm): correlation between histology,T2 and diffusion-weighted imaging

Objective:

To evaluate the capacity of diffusion-weighted imaging (DWI) to determine the histological grade of small-sized hepatocellular carcinomas (HCCs) in liver cirrhosis in comparison with T₂ weighted imaging.

Methods:

51 cirrhotic patients with 63 histologically proven HCCs ≤2 cm underwent abdominal MRI, including DWI (b-values 50, 400 and 800 s mm⁻²) and T₂ weighted sequences. HCCs were classified into well-differentiated HCCs (n = 37) and moderately differentiated HCCs (n = 26). Relative contrast ratios (RCRs) between the lesions and the surrounding liver were performed and compared between the two groups for T₂ weighted images, each b-value and apparent diffusion coefficients (ADCs). A receiver operating characteristic (ROC) analysis was performed to compare RCRs in T₂ and diffusion-weighted images.

Results:

We found significant differences in RCRs between well-differentiated vs moderately differentiated HCCs for b = 50, 400 and 800 s mm⁻² and T₂ weighted images (1.35 ± 0.36 vs 1.86 ± 0.62; 1.35 ± 0.38 vs 1.82 ± 0.60; 1.27 ± 0.30 vs 1.74 ± 0.53; 1.14 ± 0.18 vs 1.43 ± 0.28, respectively; p < 0.001), whereas no significant differences were observed in ADC and ADC RCR (1.05 ± 0.19 vs 0.99 ± 0.15 and 1.1 ± 0.22 vs 1.09 ± 0.23; p = 0.16 and p = 0.82, respectively). No significant difference was found in the areas under the ROC curve for RCRs of T₂ weighted images and every DWI b-value (p = 0.18).

Conclusion:

The RCR measurement performed in DWI 50, 400 and 800 b-values and T₂ demonstrated a significant difference between well-differentiated and moderately differentiated small-sized HCCs. Furthermore, no difference was shown by using either ADC or ADC RCR.

Advances in knowledge:

DWI with RCR measurement may be a valuable tool for non-invasively predicting the histological grade of small HCCs.Recent advances in liver imaging techniques and a better understanding of imaging findings have facilitated the detection of small nodules in cirrhotic livers. Nodular lesions ≤2 cm against a background of cirrhosis are diagnostically challenging in daily practice.¹ The early and accurate diagnosis of hepatocellular carcinomas (HCCs) is of great importance because the best treatment results are obtained in patients with small and non-invasive HCCs.^2,3 If small HCCs are not treated, they can grow aggressively and microscopic vascular invasion can occur before the 2-cm cut-off size for small HCCs.¹ Fukuda et al⁴ reported that moderately and poorly differentiated HCCs ≤2 cm have a greater tendency towards microvascular invasion, meaning that the malignant potential of small HCCs should also be taken into account when selecting a treatment. Therefore, the accurate distinction of well-differentiated HCCs from less well-differentiated HCCs is also considered an important issue in planning of the therapeutic strategy, even if the tumour is small.^5,6 Considering that histological confirmation of small suspicious hepatic nodules before treatment is often not possible owing to their location in the liver or the risks of track seeding, the role of a non-invasive pre-operative imaging technique for the discrimination of moderate to poorly differentiated HCCs from well-differentiated HCCs is important. Diffusion-weighted imaging (DWI) allows the characterization of microscopic proton displacement and has profoundly improved oncological imaging. Owing to the recent advances in MRI technology, DWI can be applied to liver imaging with improved image quality.⁷ Several clinical trials have demonstrated the benefit of DWI in the detection and characterization of focal liver lesions.^8–11 There have been attempts to correlate DWI findings with the histological grading of HCCs using signal intensity (SI) and apparent diffusion coefficient (ADC) values, but no consensus in the results was obtained.^12–18 To the best of our knowledge, the interplay between DWI and histopathological factors in a cohort of patients with exclusively small HCCs (<2 cm) has not been specifically investigated. The purpose of the present study was to investigate whether or not diffusion-weighted (DW) images and ADC could determine the histological grading of HCCs <2 cm in diameter.     

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.     

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.