Cardiac MR enables diagnosis in 90% of patients with acute chest pain,elevated biomarkers and unobstructed coronary arteries

Objective:

To assess the diagnostic value of cardiac MRI (CMR) in patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram.

Methods:

This study included a total of 125 patients treated in the chest pain unit during a 39-month period. Each included patient underwent MRI within a median of 3 days after cardiac catheterization. The MRI protocol comprised cine, oedema-sensitive and late gadolinium-enhancement imaging. The standard of reference was a consensus diagnosis based on clinical follow-up and the synopsis of all clinical, laboratory and imaging data.

Results:

MRI revealed a multitude of diagnoses, including ischaemic cardiomyopathy (CM), dilated CM, myocarditis, Takotsubo CM, hypertensive heart disease, hypertrophic CM, cardiac amyloidosis and non-compaction CM. MRI-based diagnoses were the same as the final reference diagnoses in 113/125 patients (90%), with the two diagnoses differing in only 12/125 patients. In two patients, no final diagnosis could be established.

Conclusion:

CMR performed early after the onset of symptoms revealed a broad spectrum of diseases. CMR delivered a correct final diagnosis in 90% of patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram.

Advances in knowledge:

Diagnosing patients with acute coronary syndrome but unobstructed coronary arteries remains a challenge for cardiologists. CMR performed early after catheterization reveals a broad spectrum of diseases with only a simple and quick examination protocol, and there is a high concordance between MRI-based diagnoses and final reference diagnoses.Acute coronary syndrome (ACS) is a common working diagnosis in emergency and chest pain units worldwide. Acute chest pain is the cardinal symptom of an ACS, but clinical findings vary among patients, ranging from mild discomfort to severe cardiac arrhythmias and sudden cardiac death. Among all patients admitted to a hospital with acute chest pain, only 30% receive a final diagnosis of ACS.¹ This is reasonable owing to the multitude of differential diagnoses for troponin-positive acute chest pain ranging from ST-elevation myocardial infarction to non-cardiac aetiologies, such as pulmonary embolism and sepsis.^2,3In addition to the examination of clinical signs and symptoms, electrocardiogram (ECG) diagnostics and troponin measurements are routinely used in ACS evaluation. Standard 12-lead ECG is a key diagnostic tool for determining which patients with suspected acute myocardial infarction should be directed to the angiography suite.⁴ However, while ST elevations may indicate myocardial infarction, they can also be owing to other serious conditions, including pericarditis, myocarditis, cardiomyopathy (CM) and congestive heart failure. Moreover, ACS can be present even without ECG changes, for example, in cases of non-ST-elevation myocardial infarction (NSTEMI) or unstable angina pectoris.^3–5Cardiac troponin measurement, especially with implementation of highly sensitive assays, plays a central role in establishing a diagnosis and stratifying risk in patients with ACS.^6,7 However, aetiological diagnosis remains challenging in cases of troponin-positive acute chest pain with either normal coronary arteries or non-flow-limiting coronary artery disease. There are many possible responsible entities, such as clot lysis and recanalization of an acute thrombotic obstruction, coronary thromboembolism, acute myocarditis, apical ballooning syndrome, coronary vasospasm, inherited thrombophilia, non-ischaemic cardiomyopathies and non-cardiac aetiologies.^3,8Cardiac MRI (CMR) does not yet have a well-established role in patients with suspected ACS and is not part of the routine clinical work-up described in the current guidelines of the European Society of Cardiology.⁹ However, increasing evidence suggests that CMR may provide incremental diagnostic value in these patients.^10–13 We have adopted CMR in the diagnostic work-up of patients with suspected ACS.The present study aimed to investigate the diagnostic value of CMR in patients with suspected ACS. As a standard of reference, we used a consensus-based final diagnosis established using clinical follow-up of up to 3 months after admission and the synopsis of all clinical, laboratory and imaging findings.     

Prognostic factors associated with a subchondral insufficiency fracture of the femoral head

Objective

The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF).

Methods

Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singh’s index, were documented. The morphological characteristics of the low-intensity band on T₁ weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre).

Results

Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values.

Conclusion

These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF.Subchondral insufficiency fractures of the femoral head (SIF) often occur in osteoporotic elderly patients [1-9]. Patients usually suffer from acute hip pain without any obvious antecedent trauma. Radiologically, a subchondral fracture is seen primarily in the superolateral portion of the femoral head [4,5,10]. T₁ weighted MRI reveal a very low-intensity band in the subchondral area of the femoral head, which tends to be irregular, disconnected and convex to the articular surface [2,4,5,7,9,11]. This low-intensity band in SIF was histologically proven to correspond with the fracture line and associated repair tissue [5,9]. Some cases of SIF resolve after conservative treatment [5,11-14]; other cases progress until collapse, thereby requiring surgical treatment [4-10,15]. The prognosis of SIF patients remains unclear.The current study investigated the risk factors that influence the prognosis of SIF based on the progression to collapse.     

Reliability and accuracy of scout CT in the detection of vertebral fractures

Objective:

The aim of the present study was to evaluate the reliability of scout CT (sCT) lateral radiograph, in terms of diagnostic accuracy and intra- and interobserver agreement in the detection of vertebral fractures (VFs).

Methods:

300 CT examinations of the thoracic and/or lumbar spine were collected and independently analysed by 3 musculoskeletal radiologists in 2 different sessions. A semi-quantitative approach was used for VF assessment on sCT, and morphometric analysis was performed when a VF was suspected. Results of multiplanar sagittal CT reconstructions interpreted by the most expert radiologist were considered as gold standard. Arthrosis was also scored. Only vertebral bodies assessable by both sCT and gold standard were considered for the analysis. Area under the receiver operating characteristic curve (AUROC), Cohen''s kappa statistic and linear-by-linear association were used for statistical analysis.

Results:

1522 vertebrae were considered (130 males and 170 females; ages, 73.0±2.8 years). 73 of 1522 (4.8%) VFs were identified in 34/300 patients (11.3%). In the detection of VFs, the sensitivity and specificity of sCT were 98.7% and 99.7%, respectively. Accuracy (AUROC=0.992±0.008), as well as interobserver agreement (k=0.968±0.008), was excellent. Intra-observer agreement was perfect (k=1.000). Performance of this method was independent of arthrosis, vertebral level and type and grade of VFs.

Conclusion:

sCT is a simple but very accurate method for the detection of VFs. It should be introduced as a spine evaluation tool for the detection of VFs in examinations that are performed for other diagnostic purposes.

Advances in knowledge:

sCT lateral radiograph is an accurate tool for the detection of VFs. This technique may be used with several advantages in clinical practice.Vertebral body crushing after minor trauma or no reported trauma is one of the most typical signs of osteoporosis. Vertebral fractures (VFs) occur more frequently and earlier than other osteoporosis-related fractures, and they are a hallmark of the disease [1]. It has been shown that more than 50% of VFs may be clinically silent [2] and therefore frequently underdiagnosed. This substantially contributes to leaving osteoporosis underestimated and undertreated.The total cost of VFs was estimated at €337 million per year in the European Union, although early prevention may reduce costs incurred through treating subsequent VFs [3]. However, the social and economic burden related to VFs is far higher, since they strongly predict risks for further fractures, even at other sites, also independently from bone densitometric criteria [4,5]. For instance, direct medical costs from fragility fractures to only the UK healthcare economy were estimated at £1.8 billion in 2000 and are expected to rise to over £2 billion by 2020, with most of these costs related to hip fracture care [6].In the past few years, several imaging techniques have been proposed for the detection of VFs [7,8]. Spine assessment with the aim of VF detection has been performed on the main basis of spine radiographs and dual-energy X-ray absorptiometry scans [9]. In the same way, several methods have been found to semi-quantitatively or quantitatively detect VFs. The visual semi-quantitative assessment on conventional spine radiographs [10] remains the most validated and used method in clinical practice; however, some authors support a combined approach of visual semi-quantitative and quantitative morphometric methods to overcome limits of single methods side by side [11,12].Imaging science and the increasing number of imaging examinations are both aiding and submerging clinical practice, providing more and more images with potential clinical information.The importance of incidental diagnosis of VFs during radiological examinations has been emphasised in the past few decades, with the literature growing exponentially. Results show that detection is still low when VFs are not the intent of the study [13,14]. Radiographs of the chest and abdomen, as well as CT sagittal multiplanar reconstructions (MPRs), have been considered [7,8,15,16] following the widespread use of CT imaging. In recent years, the opportunity to screen for VFs on ancillary sequences of advanced imaging techniques, such as localisation scans of CT and MRI, were also investigated [17–19]. A quick spine assessment using these underrated imaging sequences may be proposed to support the call for a systematic evaluation of the spine and the need to recognise osteoporosis early.The aim of the present study was to evaluate the reliability of scout CT (sCT) lateral radiograph, in terms of diagnostic accuracy and intra- and interobserver agreement in the detection of VFs.     

Prediction of incident hip fracture by femoral neck bone mineral density and neck-shaft angle: a 5-year longitudinal study in post-menopausal females

Objective

To compare hip fracture incidence in post-menopausal females who were differently stratified for the fracture risk according to bone mineral density and proximal femur geometry.

Methods

In a 5 year follow-up study, the hip fracture incidence in 729 post-menopausal females (45 of whom suffered from incident hip fracture) was assessed and compared. Forward logistic regression was used to select independent predictors of hip fracture risk, including age, age at menopause, height, weight, femoral neck bone mineral density (FNBMD), neck–shaft angle (NSA), hip axis length, femoral neck diameter and femoral shaft diameter as covariates. Fracture incidence was then calculated for the categories of young/old age, high/low FNBMD and wide/narrow NSA, which were obtained by dichotomising each hip fracture independent predictor at the value best separating females with and without a hip fracture.

Results

The hip fracture incidence of the whole cohort was significantly higher in females with a wide NSA (8.52%) than in those with a narrow NSA (3.51%). The combination of wide NSA and low FNBMD had the highest hip fracture incidence in the whole cohort (17.61%) and each age category. The combinations of narrow/wide NSA with low/high FNBMD, respectively, gave a significantly higher fracture incidence in older than in younger women, whereas women with a combined wide NSA and low FNBMD had no significantly different fracture incidence in young (14.60%) or old age (21.62%).

Conclusion

Our study showed that NSA is effective at predicting the hip fracture risk and that the detection in early post-menopause of a wide NSA together with a low FNBMD should identify females at high probability of incident hip fracture.Hip fracture is the most clinically relevant osteoporotic fracture because it is expensive to treat and has severe consequences [1,2]. Bone mineral density (BMD) measurement at the hip is the strongest predictor of hip fracture [3]. Despite the statistically significant relationship between the femoral neck bone mineral density (FNBMD) and the risk of hip fracture [4], its ability to predict hip fragility fracture does not seem accurate enough for diagnostic purposes [5]. Therefore, hip fragility fracture predictors besides BMD are needed to identify people at risk for fracture prevention [6]. Among these predictors, proximal femur geometry (PFG) parameters have also been proposed, as bone shape adjusts the transmission of the impact forces through the bone, contributing, together with bone structure, to determine the effective stress within the bone [7]. This topic has been largely addressed by using dual energy X-ray absorptiometry (DXA) scans since Beck et al [8] showed the relationship between DXA bone mineral density and femoral neck strength, and Faulkner et al [9] described the association between the hip axis length (HAL) measured by DXA scans and the hip fracture risk. The PFG parameters that have been reported to predict effectively hip fracture independently of BMD are HAL and neck–shaft angle (NSA) [9-18].The majority of these studies are nevertheless cross-sectional [10,12,13], and their results might not have such strong statistical evidence as those derived from longitudinal studies [9,17,18]. In addition, there are some discrepancies among authors about the best PFG parameter to predict the hip fracture risk [19-23]. The aims of this study were therefore to assess and compare in a longitudinal observation the ability of PFG parameters to separate post-menopausal females with hip fracture from those without fracture, and to assess how PFG parameters and BMD are associated with hip fracture incidence, and whether a combination of the two can identify subjects at higher risk of fracture.     

The intravertebral cleft in benign vertebral compression fracture: the diagnostic performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI

We compared the diagnostic performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI (CEMRI) in diagnosing intravertebral clefts in benign vertebral compression fractures (VCFs). We retrospectively reviewed 99 consecutive patients who had undergone percutaneous vertebroplasty for VCFs. A cleft was defined as a signal void or hyperintense area on non-enhanced MRI (T₁ and T₂ weighted imaging) or as a hypointense area within a diffusely enhanced vertebra on CEMRI. A cleft was confirmed as a solid opacification on post-procedural radiographs. The interobserver reliability and MRI diagnostic performance were evaluated. The interobserver reliability of non-enhanced MRI was substantial (k _ 0.698) and the interobserver reliability of CEMRI was almost perfect (k _ 0.836). Post-procedural radiographs showed solid cleft opacification in 32 out of the 99 cases. The sensitivity and specificity of non-enhanced MRI were 0.72 and 0.82 (observer 1) and 0.63 and 0.87 (observer 2), respectively. The sensitivity and specificity of CEMRI were 0.94 and 0.63 (observer 1) and 0.85 and 0.60 (observer 2), respectively. The sensitivity of CEMRI was significantly higher than that of non-enhanced MRI, and the specificity of non-enhanced MRI was higher than that of CEMRI. CEMRI was highly reliable and sensitive, and non-enhanced MRI was specific for intravertebral clefts. Therefore, spine MRIs, including CEMRI, could provide useful information about intravertebral clefts before percutaneous vertebroplasty.Intravertebral clefts associated with vertebral compression fractures (VCFs) are radiographic signs representing cavities within fractured vertebrae and have long been considered pathognomonic for avascular necrosis of the spine (Kümmell’s sign) [1–3]. However, several investigators have observed that intravertebral clefts are common in patients with osteoporotic compression fractures [4–6]. Currently, clefts are thought to represent corticocancellous disruption in mobile osteoporotic fractures, rather than avascular necrotic disease [4, 6].Percutaneous vertebroplasty (PV) is an effective and minimally invasive procedure for the treatment of osteoporotic compression fractures [7, 8]. The advent of PV as the major treatment option for VCFs has prompted interest in intravertebral clefts occurring in benign VCFs. Recent studies have suggested that the clinical outcomes and complications associated with PV are influenced by the presence of clefts [4, 9–13]. Thus, radiological detection of clefts is indispensable for managing patients with VCFs.Spine MRI is commonly used for the evaluation of acute VCFs. MRI is useful in distinguishing malignancy from acute osteoporotic VCFs [14, 15] and is effective in demonstrating bone marrow oedema associated with acute compression fractures, which is one of the indications for performing PV [14, 16]. The MRI findings associated with intravertebral clefts have been well described [3–5]. However, there is controversy concerning the efficacy of MRI in diagnosing clefts. Specifically, the reliability and effectiveness of contrast-enhanced MRI (CEMRI), first assessed by Oka et al in 2005 [11], has not been properly evaluated. Such evaluation is important, given that CEMRI entails additional expense.To evaluate the efficacy of the CEMRI for the prediction of intravertebral clefts, we assessed the interobserver reliability and diagnostic performance of non-enhanced T₁ weighted and T₂ weighted MRI (T1WI and T2WI) and CEMRI in the identification of intravertebral clefts in VCFs. We then compared the diagnostic performance of CEMRI with that of non-enhanced MRI.     

Quantitative pixelwise myocardial perfusion maps from first-pass perfusion MRI

Objective:

To calculate and evaluate absolute quantitative myocardial perfusion maps from rest first-pass perfusion MRI.

Methods:

10 patients after revascularization of myocardial infarction underwent cardiac rest first-pass perfusion MRI. Additionally, perfusion examinations were performed in 12 healthy volunteers. Quantitative myocardial perfusion maps were calculated by using a deconvolution technique, and results were compared were the findings of a sector-based quantification.

Results:

Maps were typically calculated within 3 min per slice. For the volunteers, myocardial blood flow values of the maps were 0.51 ± 0.16 ml g⁻¹ per minute, whereas sector-based evaluation delivered 0.52 ± 0.15 ml g⁻¹ per minute. A t-test revealed no statistical difference between the two sets of values. For the patients, all perfusion defects visually detected in the dynamic perfusion series could be correctly reproduced in the maps.

Conclusion:

Calculation of quantitative perfusion maps from myocardial perfusion MRI examinations is feasible. The absolute quantitative maps provide additional information on the transmurality of perfusion defects compared with the visual evaluation of the perfusion series and offer a convenient way to present perfusion MRI findings.

Advances in knowledge:

Voxelwise analysis of myocardial perfusion helps clinicians to assess the degree of tissue damage, and the resulting maps are a good tool to present findings to patients.MRI is widely used for the evaluation of myocardial perfusion. Advantages of perfusion MRI are a higher spatial resolution compared with positron emission tomography (PET)^1,2 and single photon emission CT³ and the lack of exposure to radiation. Great efforts have been made to use MRI for quantitative evaluation of myocardial perfusion in the past years.^4,5 In clinical routine, however, evaluation of MRI perfusion examinations is performed by the visual analysis of the acquired images depicting areas remaining hypo-intense during the passage of the contrast agent bolus. One main reason for not quantifying myocardial perfusion is the sometimes-excessive user interaction time required for manual segmentation of the acquired images in the quantification process.If myocardial perfusion is quantified, in most studies, the high spatial resolution of the acquired MR images is not maintained. Instead, a sector-based evaluation is performed.^6,7 First attempts have been made to calculate myocardial perfusion maps to evaluate regional myocardial perfusion.^3,8–10 However, until now, these studies were performed in animals^8–10 or perfusion was only evaluated semiquantitatively.³ Recently, our group has published an automatic post-processing tool for quantitative perfusion evaluation.¹¹ That study focused on the automation of post-processing but confined itself on sectors of the myocardium. The next and consequent step is to evolve this technique to work on a pixel-by-pixel basis. Therefore, it was the goal of this study to develop and test a method that calculates pixelwise quantitative perfusion maps from myocardial perfusion MRI examinations. These maps might help the clinician in making a diagnosis by decreasing the number of images to be examined, because a pixelwise quantitative perfusion map demonstrates the information of a whole series of images obtained in a first-pass perfusion examination clearly arranged.     

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.     

Semi-automated and automated glioma grading using dynamic susceptibility-weighted contrast-enhanced perfusion MRI relative cerebral blood volume measurements

Objective

Despite the established role of MRI in the diagnosis of brain tumours, histopathological assessment remains the clinically used technique, especially for the glioma group. Relative cerebral blood volume (rCBV) is a dynamic susceptibility-weighted contrast-enhanced perfusion MRI parameter that has been shown to correlate to tumour grade, but assessment requires a specialist and is time consuming. We developed analysis software to determine glioma gradings from perfusion rCBV scans in a manner that is quick, easy and does not require a specialist operator.

Methods

MRI perfusion data from 47 patients with different histopathological grades of glioma were analysed with custom-designed software. Semi-automated analysis was performed with a specialist and non-specialist operator separately determining the maximum rCBV value corresponding to the tumour. Automated histogram analysis was performed by calculating the mean, standard deviation, median, mode, skewness and kurtosis of rCBV values. All values were compared with the histopathologically assessed tumour grade.

Results

A strong correlation between specialist and non-specialist observer measurements was found. Significantly different values were obtained between tumour grades using both semi-automated and automated techniques, consistent with previous results. The raw (unnormalised) data single-pixel maximum rCBV semi-automated analysis value had the strongest correlation with glioma grade. Standard deviation of the raw data had the strongest correlation of the automated analysis.

Conclusion

Semi-automated calculation of raw maximum rCBV value was the best indicator of tumour grade and does not require a specialist operator.

Advances in knowledge

Both semi-automated and automated MRI perfusion techniques provide viable non-invasive alternatives to biopsy for glioma tumour grading.MRI is an important tool for the diagnosis of brain tumours; however, despite its established role, histopathological assessment forms the basis of prognosis calculation and treatment planning in most cases, especially for the glioma group [1-6]. Recently developed radiology-based techniques have been utilised to accurately grade intra-axial tumours, avoiding the need for time-consuming and invasive histopathological examination. These techniques include dynamic susceptibility-weighted contrast-enhanced perfusion MRI parameters such as cerebral blood flow [7-10], and metabolic measurements such as the choline–creatine ratio [11], as well as relative cerebral blood volume (rCBV) [12-17].One of the most promising and least intrusive of these new techniques uses rCBV measurements following intravenous contrast injection. rCBV is expected to correlate with tumour grade as it has been correlated with vascular endothelial growth factor expression and thus probable angiogenic ability [18]. Two main techniques have been used to measure rCBV in tumours: region of interest (ROI) analysis and histogram analysis. In ROI analyses, small ROIs are chosen by experienced radiologists in areas representing the maximum perfusion of the tumour, while avoiding artefacts such as large vessels. Good correlation with tumour grade has been observed [12,13], and this technique can also help differentiate oligodendroglioma from astrocytoma [14,15]. Histogram analyses similarly utilise experienced radiologists to draw a large analytical region around the tumour margins. All pixels contained within it are analysed to calculate various statistical values, which have also been shown to correlate with tumour grade [16,17,19,20].The primary limitation of a ROI analysis is the labour-intensive nature of finding the maximum rCBV value (rCBV_max) in the ROI and differentiating this from a possible vessel-perfusion effect, which requires the skills of a specialist. For a histogram analysis, vessel perfusion skews results, as has been shown in a recent study in which vessels were either included or excluded during ROI placement [21].We have developed easy-to-use analysis software capable of both semi-automated and automated glioma grading using ROI and histogram analyses based on perfusion scans. Our program is designed to enable non-specialists to perform the analysis, removing the need for a neuroradiologist operator, and to avoid the skewing effect of tumour vessels. The correlation of tumour parameters, calculated with the software, to glioma grade is determined using patient data previously classified from histology.     

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.     

Optimised z-axis coverage at multidetector-row CT in adults suspected of acute appendicitis

Objective:

To compare diagnostic performances of two reduced z-axis coverages to full coverage of the abdomen and pelvis for the diagnosis of acute appendicitis and alternative diseases at unenhanced CT.

Methods:

This study included 152 adults suspected of appendicitis who were enrolled in two ethical committee-approved previous prospective trials. Based on scans covering the entire abdomen and pelvis (set L), two additional sets of images were generated, each with reduced z-axis coverages: (1) from the top of the iliac crests to the pubis (set S) and (2) from the diaphragmatic crus to the pubis (set M). Two readers independently coded the visualisation of the appendix, measured its diameter and proposed a diagnosis (appendicitis or alternative). Final diagnosis was based on surgical findings or clinical follow-up. Fisher exact and McNemar tests and logistic regression were used.

Results:

46 patients had a definite diagnosis of appendicitis and 53 of alternative diseases. The frequency of appendix visualisation was lower for set S than set L for both readers (89% and 84% vs 95% and 91% by Readers A and B, respectively; p=0.021 and 0.022). The probability of giving a correct diagnosis was lower for set S (68%) than set L (78%; odds ratio, 0.611; p=0.008) for both readers, without significant difference between sets L and M (77%, p=0.771); z-axis coverage being reduced by 25% for set M.

Conclusion:

Coverage from diaphragmatic crus to pubis, but not focused on pelvis only, can be recommended in adults suspected of appendicitis.

Advances in knowledge:

In suspected appendicitis, CT-coverage can be reduced from diaphragmatic crus to pubis.CT is a well-established diagnostic tool in patients suspected of acute appendicitis because of its availability, high reproducibility, excellent diagnosis performance and low discomfort [1,2]. Since the emergence of multidetector-row CT (MDCT), the ability to rapidly scan large ranges along the z-axis makes it tempting to scan the entire abdomen and pelvis in all patients suspected of any abdominal disorder in order to also detect any alternative and/or additional diseases [3–5]. As individuals suspected of acute appendicitis are generally young—with a mean age approximating 30 years [6]—radiation dose is of particular concern, and all effort should be made to restrict exposure to the absolute minimum required for sufficient diagnosis.Limiting z-axis coverage is an easy way to reduce the radiation dose [7]. High diagnostic performance of pelvic- and appendiceal-focused CT has been reported for acute appendicitis [2,8–13], but only two studies have compared appendiceal-focused CT with scans on the entire abdomen and pelvis [2,13]. However, these studies used various administration protocols involving intravenous (IV) and enteric contrast material, preventing us generalising their results. A third study has reported that limiting CT acquisition to the pelvis could result in 7% of missed alternative diseases because of their location. In this study, the readers classified the anatomic location of CT abnormalities as abdominal (above the iliac crest) or pelvic (below the iliac crest) [8]. Finally, a very recent study by Pooler et al [14] assessed CT in the diagnosis of alternative diseases in 1571 patients suspected of acute appendicitis. The authors advocated that the appendix itself as well as alternative diseases may not be demonstrated by CT acquisition limited to the pelvis. Therefore, they suggested an investigation of the rates of alternative diagnosis detectable at focused pelvic CT.We hypothesised that an optimal z-axis coverage ranging from the diaphragmatic crus (easily seen on the frontal scout view and at least 2 cm above the top of the kidney) to the upper aspect of the pubic symphysis would allow us to accurately diagnose acute appendicitis as well as alternative diseases with substantial dose reduction compared with scanning the entire abdomen and pelvis (i.e. from the top of the liver to the lowest part of the ischiopubic branches). This coverage will be referred to in this paper as “restricted abdominal coverage”. The purpose of this study, therefore, was to compare two types of reduced coverage (the restricted abdominal coverage as defined above and that focused on the pelvis only) to coverage that included the entire abdomen and pelvis and to evaluate the diagnostic performance of each for acute appendicitis and alternative diseases.     

Functional MRI compliance in children with attention deficit hyperactivity disorder

PURPOSE

We aimed to test the effect of prescan training and orientation in functional magnetic resonance imaging (fMRI) in children with attention deficit hyperactivity disorder (ADHD) and to investigate whether fMRI compliance was modified by state anxiety.

METHODS

Subjects included 77 males aged 6–12 years; there were 53 patients in the ADHD group and 24 participants in the healthy control group. Exclusion criteria included neurological and/or psychiatric comorbidities (other than ADHD), the use of psychoactive drugs, and an intelligence quotient outside the normal range. Children were individually subjected to prescan orientation and training. Data were acquired using a 1.5 Tesla scanner and an 8-channel head coil. Functional scans were performed using a standard neurocognitive task.

RESULTS

The neurocognitive task led to reliable fMRI maps. Compliance was not significantly different between ADHD and control groups based on success, failure, and repetition rates of fMRI. Compliance of ADHD patients with extreme levels of anxiety was also not significantly different.

CONCLUSION

The fMRI compliance of ADHD children is typically lower than that of healthy children. However, compliance can be increased to the level of age-matched healthy control children by addressing concerns about the technical and procedural aspects of fMRI, providing orientation programs, and performing on-task training. In patients thus trained, compliance does not change with the level of state anxiety suggesting that the anxiety hypothesis of fMRI compliance is not supported.Functional magnetic resonance imaging (fMRI), which uses blood oxygen level-dependent contrast, is a noninvasive procedure for imaging regional brain activity. MRI exhibits high spatial resolution; even 1.5 Tesla (T) imaging used in standard clinical practice (spatial resolution of 2–4 mm) yields robust functional signal changes (1). MRI can be performed without the ethical concerns associated with the other available imaging techniques and can thus be used in children and in healthy populations. In healthy volunteers, fMRI has produced reproducible findings across scanning sites and age groups with respect to the localization and development of cognitive processes (2). Its capacity for noninvasive imaging of the brain in vivo during cognitive processing has made fMRI an exciting tool for laboratory research, as well as clinical studies and clinical practices that involve diagnosis, follow-up, and presurgical mapping (3, 4).A disorder that attracts a great deal of attention in children is attention deficit hyperactivity disorder (ADHD). This focused attention is partly due to the high incidence (0.2%–12.2%) of ADHD, which is also the most frequent diagnosis in children referred to child psychiatry departments (5–7). From the neuropsychological point of view, ADHD is associated with deficits in executive functions (8, 9). Nevertheless, as the number of theories on the subject demonstrates, ADHD remains an unresolved issue, especially with respect to its biological basis and brain correlates (10).With its many merits, fMRI would be a valuable tool for studying the etiology, diagnosis, and follow-up of ADHD patients. However, MRI is movement-sensitive, and movement artifacts impair the diagnostic quality of the examination and can even render the scans unusable. A meta-study involving 21 000 cases, reported an overall artifact frequency of 40% (11). Normal body pulsations accounted for 7%–12% of the artifacts, but at least 10% were due to motoric unrest or restlessness. In another study, artifacts other than normal body pulsations were reported in 12.8% of the scans and 6.4% of the scans were impaired in diagnostic quality (12).The symptoms of ADHD include hyperactivity, impulsivity, and inattention (13). Of these symptoms, the first two directly challenge the immobility requirement of MRI, and the third poses a problem for the task-appropriate responses that cognitive tasks require for functional imaging. Not unexpectedly, the fMRI compliance of ADHD patients is poor. In 7–12-year-old unmedicated ADHD patients, the frequency of successful runs was 77%, and the success rate for the completion of the total fMRI battery was 50%, while the values for age-matched healthy volunteers were 96% and 88%, respectively (14).Artifacts other than those caused by organ pulsations have been associated with anxiety or anxiety-sensitivity (15). Medium-to-severe anxiety was reported in 25%–37% of adults undergoing MRI (16, 17). Up to 30% exhibited anxiety-related reactions that ranged from apprehension to a reaction level severe enough to interfere with performance (18). MRI artifacts were also related to the degree of fear and/or panic and anxiety disorders such as claustrophobia (16, 19).A group of studies rejected the contribution of anxiety and proposed another set of causal factors for the artifacts and the resulting fMRI incompliance. According to these studies, patient distress can be predicted from the degree of claustrophobia but not from anxiety sensitivity per se (16). An analytical study (12) measured state anxiety using the Spielberger State-Trait Inventory (STAI), a tool commonly used for measuring state anxiety (20). In their study, state anxiety did not account for the development of movement artifacts. The artifacts were found to be associated with prescan concerns about the technical apparatus and with the procedural aspects of imaging; these concerns were focused on the narrowness of space, noise, immobility, and scan duration. The concerns, which were rated as hardly bearable, were identified in 70.6% of all individuals developing movement artifacts.An approach for meeting the concerns about the technical and procedural aspects focuses on patient comfort and cooperation. In ADHD patients, the effect of individualized prescan preparation was investigated using operant-contingency-based procedures where immediate verbal feedback was provided on response accuracy and where positive reinforcement (verbal praise) was delivered upon criterion achievement (21). This prescan preparation reduced the extent of head movements in both ADHD patients and healthy controls. However, the approach was time-consuming and, due to the sample size (n= 4), too small to be generalizable. Another approach adopted a systematically administered prescan orientation and training program (22). The study reported an overall success rate of approximately 80% in normal children and adolescents (age range, 5–18 years). Based on these findings, the study concluded that it is feasible to conduct large-scale fMRI studies in children. To our knowledge, the effect of such prescan preparations on fMRI compliance has not yet been investigated in children with ADHD.In this study we aimed to demonstrate whether prescan training and orientation affect fMRI compliance of children with ADHD and determine whether this compliance is modified by state anxiety. The study used a well-known cognitive task in the neuropsychology literature, with well-documented activation patterns in the brain.     

Differentiating benign and malignant salivary gland tumours: diagnostic criteria and the accuracy of dynamic contrast-enhanced MRI with high temporal resolution

Objective:

To determine the optimal diagnostic criterion of dynamic contrast-enhanced MRI (DCE-MRI) for predicting salivary gland malignancy using a dynamic sequence with high temporal resolution, as well as the accuracy of this technique.

Methods:

The DCE-MRI findings of 98 salivary gland tumours (74 benign and 24 malignant) were reviewed. MR images were sequentially obtained at 5-s intervals for 370 s. Two parameters, peak time and washout ratio (WR) were determined from the time–signal intensity curve. The optimal thresholds of these parameters for differentiating benign and malignant tumours were determined, along with the diagnostic accuracy of the criterion using these thresholds.

Results:

A peak time of 150 s and a WR of 30% were identified as optimal thresholds. As the criterion for malignancy, the combination of peak time <150 s and WR <30% provided a sensitivity of 79% (19/24), specificity of 95% (70/74) and an overall accuracy of 91% (89/98). Three of the five false-negative cases were malignant lymphomas of the parotid gland.

Conclusion:

Peak time <150 s with WR <30% comprised the optimal diagnostic criterion in predicting salivary gland malignancy, providing a sensitivity of 79% and specificity of 95%. The use of high temporal resolution might improve the accuracy of DCE-MRI.

Advances in knowledge:

Although several studies have reported the usefulness of DCE-MRI in the differential diagnosis of salivary gland tumours, the specific diagnostic criteria employed have differed widely. We determined the optimal criterion and its accuracy using a dynamic sequence with high temporal resolution.Salivary gland tumours account for approximately 3% of all tumours.¹ They can arise from any salivary gland, although the majority occur in the parotid gland.² Pre-operative differential diagnosis between benign and malignant salivary gland tumours is very important because the results strongly affect surgical treatment planning. Among various imaging techniques, MRI is now the modality of choice for evaluation of suspected salivary gland tumours.^3,4 Owing to its superb contrast resolution and multiplanar facilities, MRI can clearly identify a tumour''s exact location and extent, as well as its relationship with neighbouring structures. On the other hand, the sensitivity of conventional MRI in predicting malignancy is known to be quite low.^5–7Several researchers reported that time–signal intensity curves (TICs) obtained by dynamic contrast-enhanced MRI (DCE-MRI) were useful in the differential diagnosis of salivary gland tumours and that the TIC characterized by early enhancement and low washout was associated with malignancy.^4,8–15However, the specific criteria involved, that is, the definition of and thresholds for the time to peak enhancement and the washout ratio (WR), have varied widely among studies. Thus, the efficacy of DCE-MRI in the differential diagnosis of salivary gland tumours has not yet been fully established. To obtain accurate TICs, a dynamic MRI sequence with high temporal resolution should be used.^6,16 However, the temporal resolution in most of the previous studies was relatively low (15–60 s),^{8–12,14,17–20} which may partly explain the inconsistencies between reports.In this study, we applied DCE-MRI with a temporal resolution of 5 s to 98 cases with salivary gland tumours. Our aims were to evaluate the TICs of these cases and to determine the optimal diagnostic criteria for DCE-MRI as well as its accuracy in differentiating benign from malignant salivary gland tumours.     

Detection of ischaemic myocardial lesions with coronary CT angiography and adenosine-stress dynamic perfusion imaging using a 128-slice dual-source CT: diagnostic performance in comparison with cardiac MRI

Objective:

We assessed the diagnostic performance of adenosine-stress dynamic CT perfusion (ASDCTP) imaging and coronary CT angiography (CCTA) for the detection of ischaemic myocardial lesions using 128-slice dual-source CT compared with that of 1.5 T cardiac MRI.

Methods:

This prospective study included 33 patients (61±8 years, 82% male) with suspected coronary artery diseases who underwent ASDCTP imaging and adenosine-stress cardiac MRI. Two investigators independently evaluated ASDCTP images in correlation with significant coronary stenosis on CCTA using two different thresholds of 50% and 70% diameter stenosis. Hypoattenuated myocardial lesions on ASDCTP associated with significant coronary stenoses on CCTA were regarded as true perfusion defects. All estimates of diagnostic performance were calculated and compared with those of cardiac MRI.

Results:

With use of a threshold of 50% diameter stenosis on CCTA, the diagnostic estimates per-myocardial segment were as follows: sensitivity, 81% [95% confidence interval (CI): 70–92%]; specificity, 94% (95% CI: 92–96%); and accuracy 93% (95% CI: 91–95%). With use of a threshold of 70%, the diagnostic estimates were as follows: sensitivity, 48% (95% CI: 34–62%); specificity, 99% (95% CI: 98–100%); and accuracy, 94% (95% CI: 92–96%).

Conclusion:

Dynamic CTP using 128-slice dual-source CT enables the assessment of the physiological significance of coronary artery lesions with high diagnostic accuracy in patients with clinically suspected coronary artery disease.

Advances in knowledge:

Combined CCTA and ASDCTP yielded high accuracy in the detection of perfusion defects regardless of the threshold of significant coronary stenosis.It is important to evaluate not only anatomical information about coronary arteries but also physiological information about myocardial perfusion for the precise assessment of coronary artery disease (CAD) [1]. Myocardial perfusion imaging (MPI) can provide haemodynamic information during exercise-induced or pharmacological stress. Single-photon emission tomography (SPECT), cardiac MRI or positron emission tomography (PET) has been extensively used for MPI [2,3]. Moreover, a normal MPI determined using these techniques carries an excellent prognosis with a low rate of cardiac events [4–6].SPECT and PET are limited in their ability to evaluate coronary artery morphology and cardiac structures. By contrast, CT MPI with coronary CT angiography (CCTA) can evaluate not only anatomical structure, including coronary artery morphology, but also myocardial perfusion status. Although radiation dose associated with CT perfusion (CTP) is a concern, recent studies have shown that exposure to radiation can be reduced using different techniques, such as high-pitch helical scan of static CTP, half-scan duration of dynamic CTP and anatomical tube current modulation [7,8]. SPECT is more frequently used than MRI as a reference standard for evaluating the diagnostic accuracy of CTP. However, Jaarsma et al [9] reported that both cardiac MRI and PET showed a significantly higher diagnostic accuracy than SPECT for detection of obstructive CAD. Among several techniques of CTP, adenosine-stress dynamic CTP (ASDCTP) using 128-slice dual-source CT (DSCT) has the advantages of quantitative analysis of myocardial blood flow (MBF) and the use of dynamic data sets [10–14]. There have been 2 previous studies of dynamic CTP using stress perfusion MRI as the reference standard [13,15], but these reports enrolled only 10 patients in the study arm evaluating dynamic CTP.The purpose of this study was to evaluate the diagnostic performance of ASDCTP using a 128-slice DSCT for the detection of myocardial perfusion defects compared with adenosine-stress cardiac MRI.     

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

Objectives

Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice.

Methods

Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator''s current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009).

Results

63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer''s GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice.

Conclusion

There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers.The term “incidental finding” may give the impression that an unexpected finding is trivial, but an incidental finding (IF) can be life-changing [1]. One definition is “a finding that has potential health or reproductive importance which is discovered in the course of conducting research, but is beyond the aims of the study” [2]. The wider use of imaging in research is making incidental imaging findings more common, and recent academic and popular press editorials have highlighted the need for better management [3,4]. Advancing research practice is controversial and has led to recent debate [5] and deadlock [6] among imaging researchers in Europe and North America.IFs are common in research imaging. Their prevalence on brain MRI was 2.7% across 16 studies involving 19 559 participants [7] and may be as high as 12.8% on body MRI [8]. Extracolonic IFs at CT colonography require further investigation, medical or surgical intervention in 5–8% [9]. There are, therefore, important implications for informed consent, clinical review of images and mechanisms for notifying the subject. For the volunteers themselves, an IF may have serious implications for health, employment, medical or life insurance, and their state of mind. Furthermore, irrelevant imaging features incorrectly identified as pathological by non-radiologically trained researchers may cause unnecessary distress.We recently reviewed UK, European and other international legal and ethical guidance on management of IFs, and limited available information on volunteers'' expectations. Current recommendations are consistent with the principles that research volunteers should be informed of how their research images will be managed, that there should be measures for identifying and acting on IFs, and information should be disclosed to the subject and his or her responsible physician in a timely, sensitive and appropriate manner [10]. However, this guidance is hard to find and ambiguous, and does not distinguish management of imaging from other types of research sample. We suspected that management of IFs varies considerably between imaging research centres, but lacked reliable data on current practice. We have therefore surveyed UK imaging researchers to determine how IFs are currently managed to provide baseline data to inform future UK practice.     

Comparison of mammography, sonography, MRI and clinical examination in patients with locally advanced or inflammatory breast cancer who underwent neoadjuvant chemotherapy

Objectives

The purpose of this study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced or inflammatory breast cancer. Each prediction method was compared with the gold standard of surgical pathology.

Methods

43 patients (age range, 25–62 years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We compared the predicted residual tumour size and the predicted response on imaging and clinical examination with residual tumour size and response on pathology. Statistical analysis was performed using weighted kappa statistics and intraclass correlation coefficients (ICC).

Results

The ICC values between predicted tumour size and pathologically determined tumour size were 0.65 for clinical examination, 0.69 for mammography, 0.78 for sonography and 0.97 for MRI. Agreement between the response predictions at mid-treatment and the responses measured by pathology had kappa values of 0.28 for clinical examination, 0.32 for mammography, 0.46 for sonography and 0.68 for MRI. Agreement between the final response predictions and the responses measured by pathology had kappa values of 0.43 for clinical examination, 0.44 for mammography, 0.50 for sonography and 0.82 for MRI.

Conclusion

Predictions of response and residual tumour size made on MRI were better correlated with the assessments of response and residual tumour size made upon pathology than were predictions made on the basis of clinical examination, mammography or sonography. Thus, the evaluation of predicted response using MRI could provide a relatively sensitive early assessment of chemotherapy efficacy.The advantages of neoadjuvant chemotherapy are multiple and it has been used widely during the past few years [1]. Its primary role is to induce tumour shrinkage and permit breast-conserving surgery, primarily in patients with advanced breast cancer [2-4]. Neoadjuvant chemotherapy allows earlier treatment of micrometastatic disease and the study of biological markers that might predict tumour response [5]. The effectiveness of chemotherapeutic agents in treating both primary breast cancer and potential metastatic disease may be enhanced by the presence of tumour neovascularity. If chemotherapy is given before surgery, while tumour vascularity remains intact, the chemotherapeutic agents may be better able to reach the tumour and thus be more effective.Neoadjuvant chemotherapy of locally advanced breast cancer (LABC) has also been shown to improve the resectability rate, offering disease-free and overall survival rates that are at least equivalent to those offered by surgery alone [6,7]. Pathological complete response (pCR) is clinically significant because it is associated with improved long-term prognosis and decreased risk of recurrence [6,8]. Decisions regarding the continuation of current regimens and the appropriate type and timing of surgery depend on the radiological and clinical assessment of residual tumour size during neoadjuvant chemotherapy [9,10]. Until now, many studies have shown that physical examinations, mammography and sonography provide suboptimal evaluations of lesion extent that do not allow accurate assessments of pathological response or residual tumour size [5^,11-13]. In the case of LABC, physical examination, mammography or sonography may be suitable for detecting the larger lesions of non-responders, but they have limited sensitivity for responders with smaller residual lesions [14,15]. For mammography, calcifications may persist or even increase in patients who respond to neoadjuvant chemotherapy [14,16,17].Many previous studies have shown that MRI is the most reliable technique for evaluating residual disease after neoadjuvant chemotherapy, although initial reports described frequent false-negatives with smaller-volume disease [18-27]. Recent studies have increased the sensitivity of MRI, with increased resolution, reduced slice thickness and lower enhancement thresholds being used to minimise the underestimation of residual disease [15^,22-27]. It is still difficult, however, to distinguish residual scarring, necrosis and fibrosis from viable residual malignancy and to predict accurate response after neoadjuvant chemotherapy, especially in responders. Few published studies have described work with patients with inflammatory breast cancer who underwent neoadjuvant chemotherapy because the incidence of this disease is very low [28,29]. The purpose of our study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced and inflammatory breast cancer. We compared each prediction method with the gold standard of surgical pathology.     

Sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region

Objectives

The use of ultrasound to guide peripheral nerve blocks is now a well-established technique in regional anaesthesia. However, despite reports of ultrasound guided epidural access via the paramedian approach, there are limited data on the use of ultrasound for central neuraxial blocks, which may be due to a poor understanding of spinal sonoanatomy. The aim of this study was to define the sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach.

Methods

The sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach was defined using a “water-based spine phantom”, young volunteers and anatomical slices rendered from the Visible Human Project data set.

Results

The water-based spine phantom was a simple model to study the sonoanatomy of the osseous elements of the lumbar spine. Each osseous element of the lumbar spine, in the spine phantom, produced a “signature pattern” on the paramedian sagittal scans, which was comparable to its sonographic appearance in vivo. In the volunteers, despite the narrow acoustic window, the ultrasound visibility of the neuraxial structures at the L3/L4 and L4/L5 lumbar intervertebral spaces was good, and we were able to delineate the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach.

Conclusion

Using a simple water-based spine phantom, volunteer scans and anatomical slices from the Visible Human Project (cadaver) we have described the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region.Ultrasound is frequently used to guide central venous cannulation [1] and peripheral nerve blocks [2,3]. However, published data suggest that it is rarely used for imaging the spine or for central neuraxial blocks (CNBs; epidural and spinal injections) [4], which is surprising considering that there are data suggesting that an ultrasound examination prior to epidural access (pre-puncture scan, preview scan or scout scan) improves technical [5-7] and clinical [7,8] outcomes and also the learning curve of obstetric epidural anaesthesia [9]. Despite these encouraging results, we believe that there are very few anaesthetists who currently perform a preview scan prior to epidural catheterisation [5,7] or real-time ultrasound-guided (USG) CNBs [6,10]. This is quite interesting considering that emergency physicians are able to interpret ultrasound images of the spine [11] and are performing lumbar puncture using ultrasound in the accident and emergency department [11,12]. Reasons for this paucity of data or a lack of interest in USG CNBs in regional anaesthesia are not clear, but the authors believe it may be due to a lack of understanding of spinal sonoanatomy. The aim of this study was to describe the sonoanatomy relevant for USG CNBs via the paramedian approach in the lumbar region.     

Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study

Objective

It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS.

Methods

High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space.

Results

Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe.

Conclusion

These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.Myalgic encephalomyelitis, or chronic fatigue syndrome (CFS), as defined by the revised diagnostic criteria of the Centers for Disease Control and Prevention, is mainly characterised by persistent or relapsing fatigue lasting for at least 6 consecutive months [1]. As the aetiology of the disorder is currently unknown, it is important to establish whether it is associated with cerebral abnormalities; however, MRI has provided conflicting results when used to search for brain abnormalities in sufferers [2].A recent, large British MRI study by Perrin et al [2] of 18 CFS patients and 9 healthy volunteers, in which the images were examined for abnormalities in brain atrophy, deep white matter hyperintensities, and cerebral blood and cerebrospinal fluid flow, reported no significant differences in brain structure between the 2 groups at either baseline or 1-year follow-up, with the authors concluding that “These results throw open the debate into whether MRI scanning can reveal diagnostic signs of CFS and clinically questions the diagnoses of CFS made on the basis of previous research conclusions.”A small number of previous cerebral MRI studies have been conducted in CFS. A 1993 study involving the comparison by two radiologists of the scans of CFS patients and of controls whom had undergone imaging because of histories of head trauma or headache reported that the former had significantly more abnormal scans than controls (27% vs 2%) [3]; abnormalities included foci of increased white matter T₂ signal in 17% of the CFS patients and ventricular or sulcal enlargement in 10%. On the other hand, a 1997 study of white matter abnormalities found no significant difference between CFS patients and controls [4]. A 1999 study involving the comparison of MR scans by two to three radiologists found, overall, no significant differences between CFS patients and healthy controls, although those CFS patients without a psychiatric diagnosis since illness onset had more brain abnormalities on T₂ weighted images (mostly small, punctate, subcortical white matter hyperintensities, predominantly in the frontal lobes) than patients with such a diagnosis [5].Brain MRI analysis using voxel-based morphometry offers advantages over the methodologies used in the above studies. It is an objective method that is not operator dependent and that does not require a priori information about the location of possible differences between groups. The technique involves spatially normalising all the MR images to the same stereotactic space (by registering each of the images to the same template image, by minimising the residual sum of squared differences between them), segmenting the grey matter from the normalised images, correcting for volume changes arising from spatial normalisation and, finally, carrying out a statistical analysis to localise differences between groups; the output from the method is a statistical parametric map that shows regions where grey matter concentration differs significantly between groups [6,7].Thus far, just one voxel-based morphometry study of CFS has been published. In this 2004 Japanese study of 16 CFS patients, reduced grey matter volume was reported in the bilateral prefrontal cortex [8]. This represents the first report of focal grey matter atrophy in the prefrontal cortex of CFS patients. There have been no attempts, until now, to replicate this finding.Here, we report the largest voxel-based morphometry study of the brain in CFS.     

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

Objectives

To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases.

Methods

72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T₁ and T₂ weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics.

Results

417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher [area under the curve (Az) = 0.96, 0.97] than Gd-EOB-DTPA image set (Az = 0.86, 0.89) or DW-MRI image set (Az = 0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ = 0.81–0.88).

Conclusions

Combining DW-MRI with Gd-EOB-DTPA-enhanced T₁ weighted MRI significantly improved the detection of colorectal liver metastases.In patients with colorectal cancer, accurate assessment of the size, location and segmental distribution of liver metastases on a per-lesion basis is critical for treatment planning [1]. Accurate depiction of the size and distribution of liver metastases helps the selection of patients to undergo radical surgery [2,3] or minimally invasive therapy, such as radiofrequency ablation (RFA) [4], chemo-embolisation or radio-embolisation [5].The image contrast in diffusion-weighted MRI (DW-MRI) is based on differences in the mobility of water between tissues [6]. In tumour tissues, such as liver metastases, water mobility is often more impeded compared with normal parenchyma. Hence, metastases appear to have high signal intensity on DW-MRI, facilitating their detection.Compared with conventional T₂ weighted imaging, DW-MRI has been found to be superior for lesion detection in the liver [7-9]. When compared with contrast-enhanced MRI, DW-MRI had a higher diagnostic accuracy compared with superparamagnetic iron oxide (SPIO)-enhanced MRI [10] and similar diagnostic accuracy compared with gadolinium contrast-enhanced imaging [11] for detecting colorectal liver metastases. DW-MRI has also been found to be more sensitive than fluorodeoxyglucose (¹⁸FDG) positron emission tomography (PET) CT [12] for the same clinical indication. In another study, combining DW-MRI with T₁ weighted imaging after liver-specific contrast medium mangafodipir trisodium (MnDPDP) administration improved the diagnostic accuracy of colorectal liver metastases detection compared with either technique alone [13].Gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; Eovist or Primovist; Bayer Schering Pharma, Berlin, Germany) is a relatively new hepatocyte-selective MR contrast medium that has been shown to be useful detecting liver metastases measuring <1 cm in diameter [14,15]. Delayed T₁ weighted imaging in the hepatocellular phase of contrast enhancement at 20 min to several hours after contrast administration demonstrates metastases as T₁ hypointense lesions against the avidly enhancing liver parenchyma.Both DW-MRI and Gd-EOB-DTPA-enhanced MRI are useful for the detection of liver metastases [7,8,14-16]. One study performed at 3 T compared the diagnostic performance of the two techniques for the identification of small (<2 cm) liver metastases [17]. Another study at 1.5 T independently compared the diagnostic performance of DW-MRI, dynamic phase MRI and hepatobiliary phase Gd-EOB-DTPA-enhanced MRI [18]. However, the possible incremental value of combining DW-MRI with Gd-EOB-DTPA-enhanced MRI for detecting colorectal metastases has not been reported. Hence, the aim of this study was to compare the diagnostic accuracy of Gd-EOB-DTPA-enhanced MRI, DW-MRI and a combination of both techniques for the detection of colorectal hepatic metastases.     

Graves' ophthalmopathy: the role of diffusion-weighted imaging in detecting involvement of extraocular muscles in early period of disease

Objective:

To evaluate involvement of the extraocular muscle (EOM) using diffusion-weighted imaging (DWI), to determine whether there is correlation with conventional orbital MRI and apparent diffusion coefficient (ADC) values in patients with Graves'' ophthalmopathy (GO).

Methods:

35 patients known clinically with GO and 21 healthy controls were studied. Patients were assessed with clinical activity scores. All subjects underwent conventional MRI and DWI study. Involvement of the EOM was evaluated. The patients were classified as involved or uninvolved on orbital MRI and their ADC values in DWI compared.

Results:

There was significant difference in the mean ADC value of all the EOMs in patients vs controls. The ADC values of all the EOMs were higher in patients. There were significant differences in ADC values between uninvolved muscles on conventional MRI and controls for the MR, SR and LR. There was no significant difference in ADC value between the two groups when considering the IR. ADC values of medial, lateral and superior rectus muscles were increased.

Conclusion:

Increased ADC values of the EOM in patients with GO suggest that EOM damage begins at a very early stage before being detected on routine orbital MRI. The routine MRI with DWI sequence will be a useful adjunct in the selection of a group of patients most likely to benefit from early treatment.

Advances in knowledge:

This study can help to evaluate the involvement of GO in early period with MRI added DWI.Graves'' ophthalmopathy (GO) is a disorder frequently associated with autoimmune thyroid diseases that involve the retro-ocular space. This disease leads to oedema and swelling resulting in proptosis and diplopia.^1,2 It is clinically relevant in 40–50% of patients with Graves'' disease and in 2–5% of patients with immune thyroiditis.³GO is usually bilateral, but it can be asymmetric or unilateral in 15% of patients.³ The exact pathogenesis of GO remains unclear. Whatever the mechanism, ultimately, the connective tissues are extensively remodelled with the enlargement of the extraocular muscles (EOMs) and orbital adipose tissues.^4,5 Patients with GO usually present symmetric, multiple EOM enlargement in both orbits, although asymmetric muscle involvement can occur. However, true unilateral orbital involvement is uncommon, occurring in only 6–10% of patients.⁶ The muscles most frequently affected are the medial and inferior rectus muscles.⁶Orbital conventional MRI is required to avoid unnecessary decompression surgery in unclear or asymmetric proptosis, in suspected optic neuropathy. MRI can detect not only the presence or absence of swollen tissue but also objectively quantify the activity of inflammation.⁷ Diffusion-weighted imaging (DWI) provides qualitative and quantitative functional information concerning the microscopic movements of water at the cellular level. It allows a non-invasive characterization of microstructural changes. DWI has become a valuable imaging method in the evaluation of certain diseases such as head and neck, liver or kidney lesions.Recently, there has been one study on evaluation of GO using MRI with DWI in literature.⁸ The goal of our study was to assess whether differences between involvement on conventional orbital MRI and apparent diffusion coefficient (ADC) values for each EOM in patients with GO compared with those in healthy controls, and to investigate effectiveness of ADC values in diagnosis of involvement of EOM.     

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

Objective

To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.

Methods

43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis.

Results

CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm.

Conclusion

CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies.Carcinoma of the urinary bladder is the most common malignancy of the urinary tract that must be ruled out in patients with haematuria with negative upper urinary tract findings [1]. Cystoscopy remains the most sensitive method of detecting bladder cancer, but has several limitations: it is an invasive procedure; it is uncomfortable in some patients and it requires sedation or anaesthesia. Conventional ultrasound (US) is one of the imaging techniques used to screen for bladder cancer, but with variable accuracy. The best results are obtained using the latest equipment and new imaging tools such as three-dimensional (3D) ultrasound [2-5]. Angiogenesis is essential to allow growth of malignancies, and the detection of tumoural neovascularisation is one of the keys of imaging modalities to achieve a definite diagnosis. CT and MRI are accurate techniques for bladder cancer detection when they are performed with the injection of intravascular contrast agents. Detection relies on the identification of bladder cancer neovascularisation and recent studies have shown high accuracy with both techniques [6,7]. The introduction of microbubble contrast agents and the development of contrast-specific software have increased the value of ultrasound in the field of oncology [8,9]. Ultrasound contrast agents are strictly intravascular and are very sensitive in revealing tumour microvascularisation, helping in the detection and characterisation of malignancies [10-13]. Recently, the behaviour of bladder cancer has been described after the administration of ultrasound contrast agent, and its diagnosis relies on the detection of hypervascular wall bladder thickening [14].The aim of our study was to retrospectively assess the value of contrast-enhanced ultrasound (CEUS) in bladder cancer detection in a selected high-risk group of patients using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.