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.     

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.     

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.     

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.     

Acute anal toxicity after whole pelvic radiotherapy in patients with asymptomatic haemorrhoids: identification of dosimetric and patient factors

Objective:

Patients with asymptomatic haemorrhoids are known to be less tolerant of radiation doses lower than known tolerance doses. In the present study, the authors sought to identify the risk factors of acute haemorrhoid aggravation after whole pelvic radiotherapy (WPRT).

Methods:

The records of 33 patients with cervical, rectal or prostate cancer with asymptomatic haemorrhoids, which were confirmed by colonoscopy before the start of radiotherapy (RT), were reviewed. Acute anal symptoms, such as anal pain and bleeding, were observed up to 1 month after RT completion. Dosimetric and patient factors were analysed, and subgroup analyses were performed.

Results:

The median induction dose for acute anal symptoms was 34.1 Gy (range, 28.8–50.4 Gy). Post-operative treatment intent showed more acute anal toxicity of patient factors (p = 0.04). In subgroup analysis, post-operative treatment intent and concurrent chemoradiotherapy were found to be related to acute anal symptoms (p < 0.01). Of the dosimetric factors, V₁₀ tended to be related to acute anal symptoms (p = 0.08).

Conclusion:

This study indicates that asymptomatic haemorrhoid may deteriorate after low-dose radiation and that patient factors, such as treatment intent and concurrent chemotherapy, probably influence anal toxicity. In patients with asymptomatic haemorrhoids, WPRT requires careful dosimetry and clinical attention.

Advances in knowledge:

The tolerance of anal canal tends to be ignored in patients with pelvic cancer who are undergoing WPRT. However, patients with asymptomatic haemorrhoids may be troubled by low radiation doses, and further studies are required.Radiotherapy (RT) is widely used for cancer treatment along with surgery and chemotherapy.^1–5 In particular, whole pelvic RT (WPRT) plays an important role in the locoregional control of pelvic lesions in cervical, rectal and prostate cancer. Although RT is an effective anticancer treatment, it can induce complications in normal organs. There are a lot of studies about radiation tolerance doses in normal organs.^6–8Intestinal problems are common complications of WPRT, whereas severe complications, such as small bowel perforation, are rare.^9,10 On the other hand, acute anal complications, such as anal pain or bleeding, tend to be ignored because of their lower severities. However, acute anal toxicity is a painful, intractable complication. Although most acute anal problems improve spontaneously after RT completion, they are difficult to resolve during RT and result in complaints from many patients. WPRT is usually administered at doses ≤50 Gy, that is, at doses generally considered safe for the anal canal,¹¹ but when patients have haemorrhoids, RT-induced anal toxicity may become problematic.Haemorrhoids are very common and the incidence of asymptomatic haemorrhoids is high.¹² If a patient has haemorrhoids before RT, in many institutions, an anal block is used empirically. Most clinicians expect anal toxicity in patients with haemorrhoids following RT, but published studies on the topic are rare.In the present study, we sought to identify the risk factors of acute anal toxicity following WPRT in patients with pelvic cancer with asymptomatic haemorrhoids.     

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.     

The effect of concurrent androgen deprivation and 3D conformal radiotherapy on prostate volume and clinical organ doses during treatment for prostate cancer

In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm³ and 41.0 cm³ (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as “short NAD” (≤3 months; SNAD) and the remaining 29 (55.3%) as “long NAD” (>3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V_40–60 values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V_50–70 values at PT-CT compared with the SNAD group. There was a significant decline in V₃₀–V₇₅ bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses.Prostate carcinoma is (in general) a hormone-sensitive disease that has been shown to significantly benefit from androgen deprivation (AD) when added to conventional radiation therapy (RT) doses of 65–70 Gy [1–7]. Results of large randomised clinical trials have demonstrated that AD significantly improves the outcome of patients with locally advanced prostatic carcinoma when treated with external beam RT with regard to local control, biochemical-free survival and freedom from distant metastases [1, 3, 5, 8–10]. Furthermore, in the studies of the European Organization for Research and Treatment of Cancer (EORTC 22961) [1, 3] and the Radiation Therapy Oncology Group (RTOG) protocol 85–31 [2], this improvement turned into a survival advantage.Neoadjuvant androgen deprivation (NAD) before RT has been demonstrated to shrink the prostate volume effectively [11, 12], and thus has became a widely accepted and essential part of locally advanced prostate cancer management. On average, the prostate gland shrinks about 20–50% of its initial volume within 3 months of NAD [11–15] and, although the rate slows down, this shrinking effect continues beyond this period [16–19] The cytoreduction in the prostate provided by NAD may lower the complication rates observed at higher RT doses by reducing the target volumes, depending on the reduced doses received by normal tissues [15, 20].A relatively long treatment interval (7–8 weeks) is usually mandated for three-dimensional conformal radiotherapy (3D-CRT) of prostate carcinoma, and the shrinkage of the prostate gland continues during this period. In this setting, it is reasonable to assume, theoretically, that there is a possibility of a larger than planned volume of surrounding critical organs that may shift into the intermediate or high-dose regions during the RT course, which may unpredictably increase the dose received by the rectum and bladder [11, 12, 21]. Based on the above assumption, we planned to evaluate prostate shrinkage during 3D-CRT in relation to NAD duration, and to investigate the possible impact of this volume reduction on the dose received by the rectum and bladder by comparing the pre- and post-treatment dose volume histograms (DVHs).     

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.     

0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers

Objective:

We report our experience in providing palliative radiotherapy (RT) to patients with head and neck cancers (HNCs). Our hypofractionated regimen, “0-7-21”, treats patients with 24 Gy in three fractions.

Methods:

Patients, disease and response data were retrieved for candidates of 0-7-21 from 2005 to 2012. Primary end points included symptom and tumour size responses to RT based on response evaluation criteria in solid tumours (RECIST) guidelines. Secondary end points included progression-free survival (PFS) within the irradiated field, overall survival (OS) and symptomatic PFS (SPFS), calculated using Kaplan–Meier method and adverse events. Cox proportional hazards regression and logistic regression were used to investigate for prognostic factors.

Results:

A total of 110 patients were included. Among the patients, 40% and 31% had complete response for symptoms and tumour size, respectively; 42% and 50% had partial response for symptoms and tumour size, respectively; and 15% had stability of symptoms and tumour size. Median 6-month OS was 51%, and PFS within the irradiated field was 39%. Planning target volume was predictive of OS (p < 0.001), PFS (p < 0.001) and SPFS (p < 0.005), while higher TNM stage was associated with poorer tumour response (p = 0.02).

Conclusion:

0-7-21 is an effective and well-tolerated palliative RT regimen for patients with HNC. There was excellent symptom and local control with acceptable toxicity profile in these patients.

Advances in knowledge:

This is the first study to describe the outcomes of 0-7-21 in treating advanced HNCs. The positive results suggest that 0-7-21 provides excellent palliation with minimal toxicity, with significantly less on-treatment time than current published palliative RT regimen.Head and neck cancer (HNC) is the sixth most common solid malignancy,¹ and the seventh leading cause of cancer death worldwide.² Up to 70% of patients present with locally advanced disease where cure is difficult to achieve.³ In these cases, palliative radiotherapy (RT) is often necessary, as these patients are highly symptomatic from their disease situated at critical locations in the upper aerodigestive tract.Currently, there is no consensus or guideline for palliative RT for patients with locally advanced HNC, unlike other clinical situations such as for patients with metastatic disease to the bone or brain or even for advanced lung cancer.^4–6 There are few retrospective reviews of the diverse schedules of palliative RT in advanced HNC. However, most of these studies use palliative therapy as a synonym for failed radical therapy. Although longer courses with higher total RT doses have been associated with marginally better outcomes in retrospective reviews,^7,8 patients not amenable to curative treatments continue to have a dismal prognosis with a median survival of 3–12 months, even with protracted treatments.^3,7,9,10 Furthermore, delivering an extended course of RT often constitutes a challenge given the poor performance status of these patients. Therefore, the question arose as to whether a shorter course of RT with a high biological effective dose would be more appropriate, assuming it offered satisfactory symptom and disease control.In our institution at the Juravinski Cancer Centre, a palliative hypofractionated RT regimen, termed “0-7-21”, is often proposed to patients with advanced incurable and unresectable HNC, especially those with poor performance status and/or multiple comorbidities or evidence of distant metastatic disease. This treatment course consists of three fractions of 8 Gy, given over 3 weeks for a total of 24 Gy. We undertook a retrospective study of our experience, analysing the efficacy of 0-7-21.     

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.     

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”.     

Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

Objective:

To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma.

Methods:

Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength.

Results:

When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence.

Conclusion:

The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed.

Advances in knowledge:

Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma.The use of low-dose-rate (LDR) brachytherapy (BT) for cervical cancer is being phased out and replaced by either high-dose-rate (HDR) or pulsed-dose-rate (PDR) BT [1–4]. At the Christie Hospital in Manchester, UK, PDR has been implemented in place of LDR for the BT component of a combined external beam (EB) and BT treatment of cervical carcinoma [4]. The Groupe Europeen de Curietherapie–European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations [5] were used to calculate the equivalent prescribed doses of PDR BT compared with those of the formerly used LDR-BT protocol [6]. Those guidelines use generic values of linear-quadratic parameters and monophasic repair kinetics. For the organs at risk (OARs), biphasic repair has become a more accurate characterisation of the repair kinetics. This is based on clinical evidence of a slow repair component for skin telangiectasia [7], oral mucosa [8] and subcutaneous fibrosis [9]. There is also more detailed knowledge of the two fast and slow components for clonogenic cells in mouse kidney [10], rat spinal cord paralysis [11], mouse pneumonitis [12,13] and pig skin early reactions [14].PDR BT uses cycles (or pulses) of 0.5–1.0 Gy given usually at 1–1.5-h intervals, and dose distributions using PDR or LDR can be made virtually identical [15]. It was shown that 1 Gy cycles at intervals of 1–3 h (varied among animal studies) resulted in similar biological effects from the same total doses delivered continuously at 0.50–0.75 Gy per hour. Higher doses per cycle and different cycle intervals resulted in deviations from equivalence because of biphasic repair, in particular for late-reacting tissues [16,17]. The therapeutic ratio of PDR vs LDR depends on cycle dose size and interval and tissue repair characteristics [α/β ratios and repair half-times (T_1/2)]. In normal tissues with a T_1/2<0.5-h component, PDR may be more damaging than LDR [18], but the effect should be reduced if the dose per cycle is <1 Gy [16,19].The present study reports calculations of LDR-equivalent PDR doses using biphasic vs monophasic repair kinetics for both the tumour and for the OAR, and the consequent implications.     

Simultaneous integrated boost to intraprostatic lesions using different energy levels of intensity-modulated radiotherapy and volumetric-arc therapy

Objective:

This study compared the dosimetry of volumetric-arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) with a dynamic multileaf collimator using the Monte Carlo algorithm in the treatment of prostate cancer with and without simultaneous integrated boost (SIB) at different energy levels.

Methods:

The data of 15 biopsy-proven prostate cancer patients were evaluated. The prescribed dose was 78 Gy to the planning target volume (PTV78) including the prostate and seminal vesicles and 86 Gy (PTV86) in 39 fractions to the intraprostatic lesion, which was delineated by MRI or MR-spectroscopy.

Results:

PTV dose homogeneity was better for IMRT than VMAT at all energy levels for both PTV78 and PTV86. Lower rectum doses (V₃₀–V₅₀) were significantly higher with SIB compared with PTV78 plans in both IMRT and VMAT plans at all energy levels. The bladder doses at high dose level (V₆₀–V₈₀) were significantly higher in IMRT plans with SIB at all energy levels compared with PTV78 plans, but no significant difference was observed in VMAT plans. VMAT plans resulted in a significant decrease in the mean monitor units (MUs) for 6, 10, and 15 MV energy levels both in plans with and those without SIB.

Conclusion:

Dose escalation to intraprostatic lesions with 86 Gy is safe without causing serious increase in organs at risk (OARs) doses. VMAT is advantageous in sparing OARs and requiring less MU than IMRT.

Advances in knowledge:

VMAT with SIB to intraprostatic lesion is a feasible method in treating prostate cancer. Additionally, no dosimetric advantage of higher energy is observed.Randomized trials have shown a gain in biochemical relapse-free survival using dose escalation for prostate cancer.¹ However, isolated local failure is still reported in nearly one-third of patients, even with higher radiotherapy (RT) doses.¹ Local recurrence is of clinical importance because a relationship has been suggested between local control, distant metastasis and survival.² It has also been demonstrated that intraprostatic failure mainly originates at the initial tumour location as a result of intrinsic resistance of a fraction of the tumour clones, which implies that selective dose escalation to the dominant intraprostatic lesion using simultaneous integrated boost (SIB) might be beneficial.³With new RT techniques, such as intensity-modulated RT (IMRT) and volumetric-arc therapy (VMAT), SIB could be delivered without increasing acute toxicity.^4–7 Several recent studies have performed dosimetric comparison of IMRT and VMAT plans in prostate cancer;^8–10 however, dosimetric evaluation of IMRT and VMAT plans delivering SIB is rare. In these studies, target volume and organs at risk (OARs) doses may vary with different treatment planning systems. Another aspect not often addressed in these planning studies is the photon energy level.^4,8,9,11 Although higher energy photons have the potential advantage of reduced attenuation with depth, this may in turn increase the risk of secondary malignancies because of the presence of neutrons generated in the accelerator head at treatment energies >8 MV.¹²Functional imaging techniques can clearly demonstrate tumour within the prostate. MRI, MR spectroscopy (MRS) and positron emission tomography are capable of demonstrating intraprostatic lesions (IPLs).¹³ The advent of combined MRI with MRS or dynamic contrast enhanced (DCE)-MRI improves the detection rate of tumours within the prostate.^13–15The aim of the present study was to make dosimetric comparisons of VMAT and 7-field IMRT with dynamic multileaf collimators (MLCs) using the Monte Carlo algorithm with XVMC code in the treatment of prostate cancer with or without SIB, which can provide improved dose calculation accuracy and has been implemented successfully in the clinical setting.^16,17 Additionally, the impact of three photon energies on target volumes, OARs and normal tissue was evaluated in IMRT and VMAT plans.     

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.     

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.