Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Mandatory imaging cuts costs and reduces the rate of unnecessary surgeries in the diagnostic work-up of patients suspected of having appendicitis.

OBJECTIVE: To evaluate whether mandatory imaging is an effective strategy in suspected appendicitis for reducing unnecessary surgery and costs. METHODS: In 2010, guidelines were implemented in The Netherlands recommending the mandatory use of preoperative imaging to confirm/refute clinically suspected appendicitis. This retrospective study included 1,556 consecutive patients with clinically suspected appendicitis in 2008-2009 (756 patients/group I) and 2011-2012 (800 patients/group II). Imaging use (none/US/CT and/or MRI) was recorded. Additional parameters were: complications, medical costs, surgical and histopathological findings. The primary study endpoint was the number of unnecessary surgeries before and after guideline implementation. RESULTS: After clinical examination by a surgeon, 509/756 patients in group I and 540/800 patients in group II were still suspected of having appendicitis. In group I, 58.5% received preoperative imaging (42% US/12.8% CT/3.7% both), compared with 98.7% after the guidelines (61.6% US/4.4% CT/ 32.6% both). The percentage of unnecessary surgeries before the guidelines was 22.9%. After implementation, it dropped significantly to 6.2% (p<0.001). The surgical complication rate dropped from 19.9% to 14.2%. The average cost-per-patient decreased by 594 from 2,482 to 1,888 (CL:-1081; -143). CONCLUSION: Increased use of imaging in the diagnostic work-up of patients with clinically suspected appendicitis reduced the rate of negative appendectomies, surgical complications and costs. KEY POINTS: • The 2010 Dutch guidelines recommend mandatory imaging in the work-up of appendicitis. • This led to a considerable increase in the use of preoperative imaging. • Mandatory imaging led to reduction in unnecessary surgeries and surgical complications. • Use of mandatory imaging seems to reduce health care costs.

Quantification of atherosclerotic plaque components using in vivo MRI and supervised classifiers.

In this work we aimed to study the possibility of using supervised classifiers to quantify the main components of carotid atherosclerotic plaque in vivo on the basis of multisequence MRI data. MRI data consisting of five MR weightings were obtained from 25 symptomatic subjects. Histological micrographs of endarterectomy specimens from the 25 carotids were used as a standard of reference for training and evaluation. The set of subjects was divided in a training set (12 subjects) and an evaluation set (13 subjects). Four different classifiers and two human MRI readers determined the percentages of calcified tissue, fibrous tissue, lipid core, and intraplaque hemorrhage on the subject level for all subjects in the evaluation set. Quantification of the relatively small amounts of calcium could not be done with statistical significance by either the classifiers or the MRI readers. For the other tissues a simple Bayesian classifier (Bayes) performed better than the other classifiers and the MRI readers. All classifiers performed better than the MRI readers in quantifying the sum of hemorrhage and lipid proportions. The MRI readers overestimated the hemorrhage proportions and tended to underestimate the lipid proportions. In conclusion, this pilot study demonstrates the benefits of algorithmic classifiers for quantifying plaque components.

Magnetic resonance imaging of atherosclerosis.

Abundant data now link composition of the vascular wall, rather than the degree of luminal narrowing, with the risk for acute ischemic syndromes in the coronary, central nervous system, and peripheral arterial beds. Over the past few years, magnetic resonance angiography has evolved as a well-established method to determine the location and severity of advanced, lumen-encroaching atherosclerotic lesions. In addition, more recent studies have shown that high spatial resolution, multisequence MRI is also a promising tool for noninvasive, serial imaging of the aortic and carotid vessel wall, which potentially can be applied in the clinical setting. Because of the limited spatial resolution of current MRI techniques, characterization of coronary vessel wall atherosclerosis, however, is not yet possible and remains the holy grail of plaque imaging. Recent technical developments in MRI technology such as dedicated surface coils, the introduction of 3.0-T high-field systems and parallel imaging, as well as developments in the field of molecular imaging such as contrast agents targeted to specific plaque constituents, are likely to lead to the necessary improvements in signal to noise ratio, imaging speed, and specificity. These improvements will ultimately lead to more widespread application of this technology in clinical practice. In the present review, the current status and future role of MRI for plaque detection and characterization are summarized.

Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging.

BACKGROUND: One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques. METHODS AND RESULTS: MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours. CONCLUSIONS: Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.

The impact of diagnostic delay on the course of acute appendicitis.

BACKGROUND: The diagnosis of acute appendicitis is often delayed, which may complicate the further course of the disease. AIMS: To review appendectomy cases in order to determine the incidence of diagnostic delay, the underlying factors, and impact on the course of the disease. METHODS: Records of all children who underwent appendectomy from 1994 to 1997 were reviewed. The 129 cases were divided into group A (diagnostic period within 48 hours) and group B (diagnostic period 48 hours or more). RESULTS: In the group with diagnostic delay, significantly more children had first been referred to a paediatrician rather than to a surgeon. In almost half of the cases in this group initial diagnosis was not appendicitis but gastroenteritis. The perforation rate in group A was 24%, and in group B, 71%. Children under 5 years of age all presented in the delayed group B and had a perforation rate of 82%. The delayed group showed a higher number of postoperative complications and a longer hospitalisation period. CONCLUSIONS: Appendicitis is hard to diagnose when, because of a progressing disease process, the classical clinical picture is absent. The major factor in diagnostic delay is suspected gastroenteritis. Early surgical consultation in a child with deteriorating gastroenteritis is advised. Ultrasonographs can be of major help if abdominal signs and symptoms are non-specific for appendicitis.

Capillary blood sampling: should the heel be warmed?

The hypothesis that capillary blood sampling is made easier by warming the heel was examined in a randomised, controlled trial of healthy newborn infants. Sampling was performed using an automated lancet with or without prior warming. The time taken to collect a standard volume of blood, the number of repeat procedures needed, and the infants' behavioural responses were measured. Eighty one procedures were studied in 57 infants. Warming produced a median rise in heel skin temperature of 4.7 degrees C. However, there were no significant differences between the warmed and unwarmed groups in any of the outcome measures. Heel skin temperature is not an important factor in capillary blood sampling. Attention should be directed towards improving sampling devices and technique.