BACKGROUND:Post-hepatectomy liver failure (PHLF) is a leading cause of mortality after major liver resection. Accurate preoperative risk assessment is essential, yet current methods have limitations. Gadoxetic acid-enhanced MRI (Gd-EOB MRI) enables both morphological and functional evaluation of the liver. The aim of this study was to evaluate the efficacy of the hepatic uptake index (HUI) obtained from routine preoperative Gd-EOB MRI for identifying patients at risk of severe PHLF. METHODS:This observational retrospective multicentre study included 292 patients who underwent major hepatectomy between 2010 and 2020 in Sweden, Denmark, and Finland. Preoperative Gd-EOB MRI was performed for each patient and the HUI, hepatic uptake index of the standardized future liver remnant (sFLR-HUI), and Model for End-Stage Liver Disease Version 3 (MELD 3) score were evaluated. Statistical analyses included logistic regression and receiver operating characteristic (ROC) curve assessment to determine cut-off values and discriminative accuracies for severe PHLF (International Study Group of Liver Surgery grades B and C). RESULTS:Among the 292 patients, 25 (8.6%) developed severe PHLF. Patients with severe PHLF had significantly lower HUI and sFLR-HUI values (P < 0.001). The HUI demonstrated superior discriminative performance for severe PHLF (area under the curve (AUC) 0.758) compared with volume-only assessments, such as the standardized future liver remnant (sFLR) (AUC 0.628). Combining the HUI with the MELD 3 score improved performance further (AUC 0.803). CONCLUSION:The HUI obtained from routine Gd-EOB MRI outperforms volume-based biomarkers (sFLR) for identification of patients at risk of severe PHLF. Incorporating image-derived functional assessments, such as the HUI, with independent biomarkers, such as the MELD 3 score, may optimize preoperative risk stratification for severe PHLF and improve outcomes after major hepatectomy.

To evaluate the advantages of including versus excluding the tumor periphery and combining diffusion-weighted imaging (DWI) with T2-weighted imaging (T2w) for outcome predictions of preoperative radio(chemo)therapy in rectal cancer. Four analysis strategies, based on two segmentation methods and two magnetic resonance imaging (MRI) sequences, were evaluated in 106 patients examined with pretreatment MRI. One segmentation method included the tumor periphery in the region of interest (ROI) encompassing the whole tumor (wROI), considered as the reference segmentation approach, and one included only the central part (cROI). Relevant radiomics imaging features were extracted from either T2w alone or from both T2w and DWI and used by a machine learning algorithm for the prediction of pathologic complete response (pCR), neoadjuvant rectal (NAR) score, and disease recurrence. The area under the curve (AUC) was the performance measure. AUCs were compared with a bootstrapping method based on 104 bootstraps. cROI applied to both T2w and DWI provided the highest numerical prediction of pCR (AUC 0.76), however, not significantly superior to the other strategies (p ≥ 0.138). cROI applied to both T2w and DWI also yielded the highest numerical prediction of NAR score (AUC 0.84), showing advantages over wROI-based analysis strategies (AUC 0.66 and 0.69; p ≤ 0.008). When compared to cROI applied to T2w alone (AUC 0.73), the benefit was borderline statistically significant (p = 0.053). For prediction of disease recurrence, no differences were found between the analysis strategies. Inclusion of the tumor periphery in radiomic analysis of magnetic resonance images does not improve predictions of the preoperative therapy response in patients with rectal cancer. Excluding tumor periphery while adding DWI to T2w improves prediction of the NAR score, although it does not affect pCR or recurrence prediction.

This study aimed to evaluate the predictive value and clinical impact of a clinically implemented artificial neural network software model. The software detects intracranial hemorrhage (ICH) from head computed tomography (CT) scans and artificial intelligence (AI)-identified positive cases are then annotated in the work list for early radiologist evaluation. The index test was AI detection by the program Zebra Medical Vision-HealthICH+. Radiologist-confirmed ICH was the reference standard. The study compared whether time benefits from using the AI model led to faster escalation of patient care or surgery within the first 24 h. A total of 2,306 patients were evaluated by the software, and 288 AI-positive cases were included. The AI tool had a positive predictive value of 0.823. There was, however, no significant time reduction when comparing the patients who required escalation of care and those who did not. There was also no significant time reduction in those who required acute surgery compared with those who did not. Among the individual patients with reduced time delay, no cases with evident clinical benefit were identified. Although the clinically implemented AI-based decision support system showed adequate predictive value in identifying ICH, there was no significant clinical benefit for the patients in our setting. While AI-assisted detection of ICH shows great promise from a technical perspective, there remains a need to evaluate the clinical impact and perform external validation across different settings.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial meta-bolic function in progression of mitral regurgitation is poorly understood. We used 11C-acetate PET to noninvasively measure myocardial mech-anical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volun-teers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquar-tile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% +/- 5.0%) was lower than in censored patients (28.5% +/- 4.5%, P = 0.002) or healthy volunteers (30.1% +/- 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent signifi-cance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve sur-gery in patients with asymptomatic moderate-to-severe or severe pri-mary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p<0.001) and showed weak but significant correlations (r2<0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p<0.05), while LVEF and NT-pro-BNP were not (p>0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Abstract Background Quantitative echocardiographic assessment of severity of primary mitral regurgitation (MR) is challenging. CMR is recommended if MR severity cannot be clearly determined, since quantitation of regurgitation as well as of left ventricular (LV) volumes and function is crucial for the indication for surgery especially in asymptomatic patients. Purpose We aimed to compare volumetric measurements obtained from transthoracic echo (TTE) and cardiovascular magnetic resonance (CMR) using ECG-gated [(11)C]acetate PET as reference for assessment of LV volumes. Methods A total of 51 asymptomatic patients with severe primary mitral regurgitation underwent TTE, CMR and PET on the same day. Mitral regurgitant volumes (RVol) were measured by TTE using proximal convergence (PISA) method and by CMR, subtracting aortic forward flow volume from LV stroke volume. LV volumes were measured by TTE, CMR and PET. Results Despite a fair correlation between regurgitant volumes measured by TTE and CMR (r=0.53, p<0.001), PISA method heavily overestimated regurgitant volumes on TTE as compared to CMR (103±60ml vs. 78±35ml, p<0.001). TTE systematically underestimated LV volumes as compared to CMR (see table) despite a good correlation (r=0.81, 0.67 and 0.76 respective for LV EDV, ESV and SV, p<0.001 for all). There was no difference in LV EF between the methods. LV volumes obtained by CMR and PET showed a strong correlation (r=0.92, 0.79 and 0.89 respective for LV EDV, ESV and SV, p<0.001 for all) and agreement (see table). Comparison of TTE, CMR and PET TTE CMR PET PET TTEvs.CMR PET CMRvs.PET F-test LV EDV, ml 145±34 241±57 234±51 <0.001 0.004 <0.001 LV ESV, ml 47±11 76±22 81±23 <0.001 0.067 <0.001L LV SV, ml 99±26 164±38 152±34 <0.001 <0.001 <0.001 LV EF, % 68±5 69±5 65±6 0.236 <0.001 <0.001 Conclusions As compared to CMR, PISA method used by TTE substantially overestimates regurgitant volumes in patients with asymptomatic primary mitral regurgitation. Conversely, LV volumes in spite of good correlation are heavily underestimated by TTE in comparison with CMR. A strong correlation and agreement between LV volumes measured by CMR and PET confirms the accuracy of the former method which is considered as a golden standard for assessment of ventricular function and volumes. Thus, even so-called quantitative echo measures should be understoas essentially semi-quantitative indicators of severity.

AIM:To evaluate integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/magnetic resonance imaging (MRI), in comparison with the standard technique, integrated 18F-FDG-PET/computed tomography (CT), in preoperative staging of oesophageal or gastroesophageal junctional cancer. MATERIALS AND METHODS:In the preoperative staging of 16 patients with oesophageal or gastroesophageal junctional cancer, 18F-FDG-PET/MRI was performed immediately following the clinically indicated 18F-FDG-PET/CT. MRI-sequences included T1-weighted fat-water separation (Dixon's technique), T2-weighted, diffusion-weighted imaging (DWI), and gadolinium contrast-enhanced T1-weighted three-dimensional (3D) imaging. PET was performed with 18F-FDG. Two separate teams of radiologists conducted structured blinded readings of 18F-FDG-PET/MRI or 18F-FDG-PET/CT, which were then compared regarding tumour measurements and characteristics as well as assessment of inter-rater agreement (Cohen's kappa) for the clinical tumour, nodal and metastatic (TNM) stage. RESULTS:There were no medical complications. Comparison of tumour measurements revealed high correlations without significant differences between modalities. The maximum standardised uptake value (SUVmax) values of the primary tumour with 18F-FDG-PET/MRI had excellent correlation to those of 18F-FDG-PET/CT (0.912, Spearman's rho). Inter-rater agreement between the techniques regarding T-stage was only fair (Cohen's kappa, 0.333), arguably owing to relative over-classification of the T-stage using 18F-FDG-PET/CT. Agreements in the assessment of N- and M-stage were substantial (Cohen's kappa, 0.849 and 0.871 respectively). CONCLUSION:Preoperative staging with 18F-FDG-PET/MRI is safe and promising with the potential to enhance tissue resolution in the area of interest. 18F-FDG-PET/MRI and 18F-FDG-PET/CT correlated well for most of the measured values and discrepancies were seen mainly in the assessment of the T-stage. These results facilitate further studies investigating the role of 18F-FDG-PET/MRI in, e.g., predicting or determining the response to neoadjuvant therapy.

A wealth of information is contained in images obtained by whole-body magnetic resonance imaging (MRI). Studying the link between the imaged anatomy and properties known from outside sources has the potential to give new insights into the underlying factors that manifest themselves in individual human morphology. In this work we investigate the expression of age-related changes in the whole-body image. A large dataset of about 32,000 subjects scanned from neck to knee and aged 44-82 years from the UK Biobank study was used for a machine-based analysis. We trained a convolutional neural network based on the VGG16 architecture to predict the age of a given subject based on image data from these scans. In 10-fold cross-validation on 23,000 of these images the network reached a mean absolute error (MAE) of 2.49 years (R 2 = 0.83) and showed consistent performance on a separate test set of another 8,000 images. On a second test set of 100 images the network outperformed the averaged estimates given by three experienced radiologists, which reached an MAE of 5.58 years (R 2 = 0.08), by more than three years on average. In an attempt to explain these findings, we employ saliency analysis that opens up the image-based criteria used by the automated method to human interpretation. We aggregate the saliency into a single anatomical visualization which clearly highlights structures in the aortic arch and knee as primary indicators of age.

BACKGROUND:Unrecognized myocardial infarctions (UMIs) are common. The study is an extension of a previous study, aiming to investigate the long-term (>5 year) prognostic implication of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) detected UMI in patients with suspected stable coronary artery disease (CAD) without previously diagnosed myocardial infarction (MI). METHODS:In 235 patients with suspected stable CAD without previous MI, LGE-CMR imaging and coronary angiography were performed. LGE with a subendocardial component detectable in more than one imaging plane was required to indicate UMI. The stenosis grade of the coronary arteries was determined, including in the artery supplying an infarcted area. Stenosis ≥70% stenosis was considered significant. Patients were followed for 5.4 years in mean regarding a composite endpoint of cardiovascular death, MI, hospitalization due to heart failure, stable or unstable angina. RESULTS:UMI were present in 58 of 235 patients (25%). Thirty-nine of the UMIs were located downstream of a significant coronary stenosis. During the follow-up 40 patients (17.0%) reached the composite endpoint. Of patients with UMI, 34.5% (20/58) reached the primary endpoint compared to 11.3% (20/177) of patients with no UMI (HR 3.7, 95% CI 2.0-6.9, p<0.001). The association between UMI and outcome remained (HR 2.3, 95% CI 1.2-4.4, p = 0.012) after adjustments for age, gender, extent of CAD and all other variables univariate associated with outcome. Sixteen (41%) of the patients with an UMI downstream of a significant stenosis reached the endpoint compared to four (21%) patients with UMI and no relation to a significant stenosis (HR 2.4, 95% CI 0.8-7.2, p = 0.12). CONCLUSION:The presence of UMI was independently associated with an increased risk of cardiovascular events during long-term follow up.

OBJECTIVES:In an elderly population, the prevalence of unrecognized myocardial infarction (UMI) scars found via late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging was more frequent than expected. This study investigated whether UMI scars detected with LGE-CMR at age 70 would be detectable at age 75 and whether the scar size changed over time.METHODS:From 248 participants that underwent LGE-CMR at age 70, 185 subjects underwent a follow-up scan at age 75. A myocardial infarction (MI) scar was defined as late enhancement involving the subendocardium.RESULTS:In the 185 subjects that underwent follow-up, 42 subjects had a UMI scar at age 70 and 61 subjects had a UMI scar at age 75. Thirty-seven (88 %) of the 42 UMI scars seen at age 70 were seen in the same myocardial segment at age 75. The size of UMI scars did not differ between age 70 and 75.CONCLUSIONS:The prevalence of UMI scars detected at LGE-CMR increases with age. During a 5-year follow-up, 88 % (37/42) of the UMI scars were visible in the same myocardial segment, reassuring that UMI scars are a consistent finding. The size of UMI scars detected during LGE-CMR did not change over time.KEY POINTS:• UMI scars detected by LGE-CMR are frequent in elderly. • The prevalence of UMI scars detected with LGE-CMR increases with age. • UMI scar size does not change over time.

Volumetric quantification of regurgitant volume in asymptomatic severe degenerative mitral regurgitation by echocardiography and cardiac mri with independent validation of forward stroke volume by positron emission tomography

Aims: Non-invasive methods like aspartate aminotransferase to platelets ratio index (APRI) score or spleen volume changes were proposed to identify patients with sinusoidal injury after preoperative chemotherapies for colorectal liver metastases. Magnetic resonance imaging flowmetry can be used to measure changes in portal vein hemodynamics in patients with sinusoidal injury. The present study evaluates the changes in portal vein flow mean velocity (VELO) after glucagon application and analyzes their ability to predict severe sinusoidal injury (SSI) in comparison to other methods. Methods: Magnetic resonance imaging flowmetry of portal vein was estimated in 28 fasting patients and repeated five minutes after 0.5 mg glucagon injection the day before liver surgery. APRI score was estimated the same day. Spleen volume changes were calculated from segmented spleen volumes on imaging before chemotherapy start and the day before surgery. Resected non-tumorous liver parenchyma was evaluated for sinusoidal injury; parenchymal extinction lesion or nodular regenerative hyperplasia was recognized as SSI. Results: SSI was observed in 6 of 28 patients. Patients with SSI demonstrated higher APRI score 0.65 vs. 0.36, p = 0.028; and non-significant change in spleen volume, 36% vs. 12%, p = 0.764. Percentage of change in VELO five minutes after glucagon in SSI patients was 11% vs. – 3%, p = 0.039. Change in VELO <= – 0.5% predicted SSI with 83% sensitivity and 73% specificity (cross-validated classification error rate 29%), similarly to APRI score >=0.43 with the same sensitivity and specificity but higher classification error rate 32%. Conclusions: Relative changes of VELO five minutes after glucagon administration showed lowered ability of portal system to react on glucagon stimuli in patients with SSI. Application of glucagon as a stress test of portal vein hemodynamic facilitates magnetic resonance imaging flowmetry ability to predict SSI non-invasively.

BACKGROUND:Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels of cardiac biomarkers, UMI and extent of CAD in patients with stable CAD. METHODS:A total of 235 patients (median age: 65years; 34% women) with stable CAD without previously known myocardial infarction were examined with late gadolinium enhancement cardiovascular magnetic resonance imaging and coronary angiography. Blood samples were drawn at enrolment and high sensitivity cardiac troponin I (cTnI), NT-proBNP and Galectin-3 were analyzed. RESULTS:UMI was detected in 58 patients (25%). The median levels of cTnI, NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renal function, cTnI remained independently associated with the presence of UMI (p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, was independently associated with UMI or extent of CAD. CONCLUSIONS:The independent association between levels of cTnI and UMI indicates a common pathophysiological pathway for the cTnI elevation and development of UMI. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov (NCT01257282).

Comparison of left ventricular volumes and regurgitant volumes by echocardiography and magnetic resonance in patients with severe degenerative mitral regurgitation

Background Individuals with unrecognized myocardial infarctions (UMIs) detected with cardiovascular magnetic resonance (CMR) constitute a recently defined group whose prognosis has not been fully evaluated. However, increasing evidence indicate that these individuals may be at considerable cardiovascular risk. The aim of the present study was to investigate the prognostic impact of CMR detected UMIs for major adverse cardiac events (MACE) in community living elderly individuals. Methods Late gadolinium enhancement CMR was performed in 248 randomly chosen 70-year-olds. Individuals with myocardial infarction (MI) scars, with or without a hospital diagnosis of MI were classified as recognized MI (RMI) or UMI, respectively. Medical records and death certificates were scrutinized. MACE was defined as cardiac death, non-fatal MI, a new diagnosis of angina pectoris, or symptom-driven coronary artery revascularization. Results During follow-up (mean 11 years) MACE occurred in 10 % ( n = 18/182) of the individuals without MI scars, in 20 % ( n = 11/55) of the individuals with UMI, and in 45 % ( n = 5/11) of the individuals with RMI, with a significant difference between the UMI group and the group without MI scars ( p = 0.045), and between the RMI group and the group without MI scars ( p = 0.0004). Cardiac death and/or non-fatal MI occurred in 15, 5, and 3 of the individuals in the NoMI, UMI, and RMI group respectively. Hazards ratios for MACE adjusted for risk factors and sex were 2.55 (95 % CI 1.20-5.42; p = 0.015) for UMI and 3.28 (95 % CI1.16-9.22; p = 0.025) for RMI. Conclusions The presence of a CMR detected UMI entailed a more than double risk for MACE in community living 70-year-old individuals.

BACKGROUND:Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD.METHODS AND FINDINGS:In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade ≥70%. In an age- and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery.CONCLUSIONS:The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR.TRIAL REGISTRATION:ClinicalTrials.gov NTC01257282.