Prospective Comparison of 18-FDG PET/CT and Whole-Body MRI with Diffusion-Weighted Imaging in the Evaluation of Treatment Response of Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant.

To compare the prognostic values of 18-FDG PET/CT (FDG-PET) and Whole-Body MRI with Diffusion-Weighted Imaging (WB-DW-MRI) in the evaluation of treatment response of Multiple Myeloma (MM) patients eligible for ASCT. Thirty patients with newly diagnosed MM prospectively underwent FDG-PET and WB-DW-MRI at baseline, after induction chemotherapy and after ASCT. Response on WB-DW-MRI was evaluated with the MY-RADS criteria. FDG-PET was considered positive if residual uptake was superior to liver uptake. Imaging results were not used for treatment modification. The impact of imaging results on PFS was analyzed. After a median follow-up of 32 months, 10 patients relapsed. With WB-DW-MRI, post-induction examination was positive in 3/25 and post-ASCT examination was positive in 3/27 patients. However, neither study showed prognostic impact on PFS. FDG-PET was positive in 5/22 post-induction and 3/26 patients post-ASCT, respectively. Positivity of FDG-PET, post-induction or post-ASCT, was associated with a shorter PFS (post-induction: median PFS 19 months vs. not reached, log-rank p = 0.0089; post-ASCT: median PFS 18 months vs. not reached, log-rank p = 0.0005). Preliminary results from this small, single-center, prospective study show that, whether performed post-induction or post-ASCT, FDG-PET has a higher prognostic value than WB-DW-MRI for treatment response evaluation of newly diagnosed MM.

Prospective comparison of 18-FDG PET/CT and whole-body diffusion-weighted MRI in the assessment of multiple myeloma.

Magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG 18F-FDG PET-CT) are standard procedures for staging multiple myeloma (MM). Diffusion-weighted sequences applied to whole-body MRI (WB-DWI) improve its sensitivity. We compared the number of MM bone focal lesions (FLs) detected by 18F-FDG PET-CT and WB-DWI and evaluated the diagnostic performance of 18F-FDG PET-CT for diffuse infiltration. Thirty newly diagnosed MM patients prospectively underwent 18F-FDG PET-CT and WB-DWI. The criteria for skeletal region positivity were ≥ 1 focal bone lesions (FLs) and/or diffuse disease. MRI with the MY-RADS criteria was used as a reference standard for the diagnosis of diffuse infiltration. 18F-FDG PET-CT and WB-DWI were both interpreted as positive in 28/30 patients with an agreement of 1.00 (95% CI 0.77-1.00) between the two methods. The mean numbers of FLs were 16.7 detected by 18F-FDG PET-CT and 23.9 detected by WB-DWI (P = 0.028). WB-DWI detected more FLs in the skull (P = 0.001) and spine (P = 0.006). Agreement assessed using the prevalence and bias-corrected kappa index was moderate (0.40-0.60) for the spine, sternum-ribs and upper limbs and substantial (0.60-0.80) for the pelvis and lower limbs. As regards the diagnosis of diffuse bone marrow infiltration, the sensitivity, specificity and accuracy of 18F-FDG PET-CT were 0.75, 0.79 and 0.77, respectively. Although WB-DWI detected more FLs than did 18F-FDG PET-CT, there was no difference in the detection of bone disease on a per-patient basis. 18F-FDG PET-CT showed high performance, including for evaluation of diffuse infiltration.

Prospective Comparison of 18F-Choline Positron Emission Tomography/Computed Tomography (PET/CT) and 18F-Fluorodeoxyglucose (FDG) PET/CT in the Initial Workup of Multiple Myeloma: Study Protocol of a Prospective Imaging Trial.

BACKGROUND: The International Myeloma Working Group recommends the use of 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for treatment response evaluation, as it is superior to magnetic resonance imaging (MRI). However, at initial staging, the sensitivity of FDG-PET remains inferior to that of MRI. Therefore, there is a need for an imaging technique that could have a sensitivity equal to that of MRI at diagnosis and could serve to evaluate therapy. 18F-choline has shown increased sensitivity when compared with 18-FDG, with about 75% more lesions detected in patients with relapsed or progressive multiple myeloma (MM). OBJECTIVE: Our primary objective is to prospectively compare the detection rate of bone lesions by 18F-choline PET/CT (FCH-PET) and FDG-PET in newly diagnosed MM. Our secondary objectives are to assess the accuracy of both PET modalities for the detection of bone lesions and the diagnosis of diffuse disease, to assess the detection rate of extramedullary lesions. METHODS: We will prospectively include 30 patients in a paired comparative accuracy study. Patients with de novo MM will undergo FCH-PET, FDG-PET, and whole-body MRI (WB-MRI) within a 3-week period. WB-MRI will be composed of conventional sequences on the spine and pelvis and of whole-body diffusion axial sequences. The following 6 skeletal areas will be defined: skull, sternum/costal grid, spine, pelvis, superior limbs, and inferior limbs. The number of focal lesions, their respective localization, and intensity of uptake will be retrieved for each skeletal area. Readings will be performed blinded from other imaging techniques. The reference standard will be WB-MRI. Focal lesions present on PET/CT but not on WB-MRI will require a decision made with a consensus of experts based on clinical and imaging data. The number of bone lesions and number of extramedullary lesions will be compared using the Wilcoxon test. The accuracy of FCH-PET and FDG-PET will be compared using the McNemar test. RESULTS: The study started in September 2019, and enrollment is ongoing. As of June 2020, 8 participants have been included. Data collection is expected to be completed in June 2021, and the results are expected to be available in December 2021. CONCLUSIONS: This study will assess if FCH-PET is superior to FDG-PET for the evaluation of MM tumor burden. This will pave the way for future prospective evaluations of the prognostic value of 18-FCH for treatment response evaluation in MM patients. Additionally, this work may provide new perspectives for better assessment of the risk of smoldering MM progressing to MM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03891914; https://clinicaltrials.gov/ct2/show/NCT03891914. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17850.

High-Resolution Late Gadolinium Enhancement Magnetic Resonance for the Diagnosis of Myocardial Infarction With Nonobstructed Coronary Arteries.

OBJECTIVES: The aim of this study was to assess the diagnostic yield of cardiac magnetic resonance (CMR) including high-resolution (HR) late gadolinium enhancement (LGE) imaging using a 3-dimensional respiratory-navigated method in patients with myocardial infarction with nonobstructed coronary arteries (MINOCA). BACKGROUND: CMR plays a pivotal role for the diagnosis of patients with MINOCA. However, the diagnosis remains inconclusive in a significant number of patients, the results of CMR being either negative or uncertain (i.e., compatible with multiple diagnoses). METHODS: Consecutive patients categorized as having MINOCA after blood testing, electrocardiography, coronary angiography, and echocardiography underwent conventional CMR, including cine, T2-weighted, first-pass perfusion, and conventional breath-held LGE imaging. HR LGE imaging using a free-breathing method allowing improved spatial resolution (voxel size 1.25 × 1.25 × 2.5 mm) was added to the protocol when the results of conventional CMR were inconclusive and was optional otherwise. Diagnoses retained after reviewing conventional CMR were compared with those retained after the addition of HR LGE imaging. RESULTS: From 2013 to 2016, 229 patients were included (mean age 56 ± 17 years, 45% women). HR LGE imaging was performed in 172 patients (75%). In this subpopulation, definite diagnoses were retained after conventional CMR in 86 patients (50%): infarction in 39 (23%), myocarditis in 32 (19%), takotsubo cardiomyopathy in 13 (8%), and other diagnoses in 2 (1%). In the remaining 86 patients (50%), results of CMR were inconclusive: negative in 54 (31%) and consistent with multiple diagnoses in 32 (19%). HR LGE imaging led to changes in final diagnosis in 45 patients (26%) and to a lower rate of inconclusive final diagnosis (29%) (p < 0.001). In particular, HR LGE imaging could reveal or ascertain the diagnosis of infarction in 14% and rule out the diagnosis of infarction in 12%. HR LGE imaging was particularly useful when the results of transthoracic echocardiography, ventriculography, and conventional CMR were negative, with a 48% rate of modified diagnosis in this subpopulation. CONCLUSIONS: HR LGE imaging has high diagnostic value in patients with MINOCA and inconclusive findings on conventional CMR. This has major diagnostic, prognostic, and therapeutic implications.

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis.

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed. A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%. In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

Relationship Between Fibrosis Detected on Late Gadolinium-Enhanced Cardiac Magnetic Resonance and Re-Entrant Activity Assessed With Electrocardiographic Imaging in Human Persistent Atrial Fibrillation.

OBJECTIVES: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF). BACKGROUND: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood. METHODS: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed. RESULTS: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m2. The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008). CONCLUSIONS: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

Inter-reader agreement in HRCT detection of pleural plaques and asbestosis in participants with previous occupational exposure to asbestos.

OBJECTIVES: To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. METHODS: The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. RESULTS: κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. CONCLUSIONS: Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.

Coronary imaging techniques with emphasis on CT and MRI.

Coronary artery imaging in children is challenging, with high demands both on temporal and spatial resolution due to high heart rates and smaller anatomy. Although invasive conventional coronary angiography remains the benchmark technique, over the past 10 years, CT and MRI have emerged in the field of coronary imaging. The choice of hardware is important. For CT, the minimum requirement is a 64-channel scanner. The temporal resolution of the scanner is most important for optimising image quality and minimising radiation dose. Manufacturers have developed several modes of electrocardiographic (ECG) triggering to facilitate dose reduction. Recent technical advances have opened new possibilities in MRI coronary imaging. As a non-ionising radiation technique, MRI is of great interest in paediatric imaging. It is currently recommended in centres with appropriate expertise for the screening of patients with suspected congenital coronary anomalies. However, MRI is still not feasible in infants. This review describes and discusses the technical requirements and the pros and cons of all three techniques.

Computer tomography in pulmonary invasive aspergillosis in hematological patients with neutropenia: an useful tool for diagnosis and assessment of outcome in clinical trials.

BACKGROUND AND OBJECTIVE: The exact timing of the evolution of lesion volumes of invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the management of hematological patients but has never been evaluated in a prospective study. We analyzed the CT scan data from the prospective Combistrat trial. DESIGN AND METHODS: Volumes of aspergillosis lesions from 30 patients (including 24 acute myeloid leukaemia) with probable (n=26) or proven (n=4) IPA according to the EORTC-MSG modified criteria, were measured prospectively on the thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of treatment (EOT). RESULTS: For the overall population, the volume of pulmonary aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p=0.003). Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with p=0.003 for D14 vs. D7, but with p=0.56 for D14 vs. D0). At EOT (= D17, median value), the volume of lesions was significantly lower than D14 (0.76 fold the initial volume; p<0.001) but it was not significantly different when compared to D0 (p=0.11). CONCLUSIONS: The results of this prospective study suggest that the sequential analysis of CT scan in neutropenic patients with IPA depicts more precisely the evolution of lesion volumes than comparison to baseline images. Moreover, the systematic use of chest CT appears to be a useful tool for diagnosis and outcome evaluation of IPA in clinical trials.

Two-dimensional strain as a marker of subclinical anterior ischaemia in anomaly of left coronary artery arising from pulmonary artery.

A 13-year-old boy was admitted to our department after an out-of-hospital cardiac arrest during physical exertion. Transitory ST-segment elevation in the anterior chest leads was noted after defibrillation. At 48 h, initial evaluation was performed. Twelve-lead EKG and telemetry were normal. Transthoracic echocardiography showed normal left ventricle (LV) size and global function. Segmental two-dimensional (2D) longitudinal strain of the anterior wall was significantly decreased when compared with the other segments, and was associated with post-systolic shortening. Coronary angiography and 64-slice computed tomography revealed an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). ALCAPA is a rare congenital malformation. The usual clinical course is a severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. In some cases, collateral blood supply from the right coronary artery is sufficient and symptoms may be subtle or even absent. However, ventricular arrhythmias or sudden cardiac death during exercise may be the first clinical presentation in patients with ALCAPA. Indirect evidence suggests that myocardial ischaemia is the underlying aetiology of cardiac ventricular ischaemia in patients with ALCAPA. Post-systolic shortening and altered longitudinal strain have recently been described as potential useful markers of ischaemic dysfunction in patients with ischaemic heart disease. In this case report, we demonstrate the usefulness of 2D strain as a non-invasive tool to assess subclinical myocardial ischaemia in patients with an ALCAPA. This provides further supportive evidence for the role of cardiac ischaemia in aetiology of ventricular arrhythmia in this rare condition.

Abnormality of venous return associated with congenital heart defect in an adult patient.

Systemic venous abnormalities are common and in some cases may be associated with congenital heart defects. We report here a case of a 67-year-old woman with bilateral superior vena cava with interruption of the inferior vena cava with hemiazygous continuation in the context of left atrial isomerism. These abnormalities were associated with a small secundum atrial septal defect and patent foramen ovale. The dilated hemiazygous vein was a potential mimicker of aortic pathology. The dilated coronary sinus was a sign of anomalous venous return. The echocardiographist should search systematically for a congenital heart defect on detection of this type of anomalous venous return. Radiological imaging can help to confirm the diagnosis.

Quantitative MRI comparison of pulmonary hemodynamics in mustard/senning-repaired patients suffering from transposition of the great arteries and healthy volunteers at rest.

In Mustard/Senning-repaired (MSR) patients, the right and left ventricles (RV, LV) act as the systemic and pulmonary ventricle, respectively. The purpose of the study was to compare non-invasively, at rest, pulmonary ventricle systolic function and hemodynamics in MSR patients with those of healthy volunteers. Velocity-encoded MR imaging was performed at the level of the main pulmonary artery (MPA) in ten male patients late after a Mustard/Senning correction performed early in infancy and in ten male volunteers. Both blood flow and MPA cross-sectional area variations were recorded over a complete cardiac cycle. MPA distensibility, body surface area (BSA)-normalized pulmonary ventricle systolic power and work were significantly lower in the MSR patients compared to volunteers. In particular, BSA-normalized LV systolic power and work in MSR patients were equal to 82 and 77% on average of those of the RV in volunteers (0.32 vs. 0.39 W/m2 and 0.10 vs. 0.13 J/m2), respectively. We conclude that in MSR patients at rest two unrelated findings were observed: (1) a reduced MPA distensibility and (2) a significantly lower systolic mechanical performance of the pulmonary LV compared to that of the RV in healthy volunteers. The latter quantification indirectly confirms the lowest systemic RV systolic mechanical performance previously published.

Feasibility of aortic pulse pressure and pressure wave velocity MRI measurement in young adults.

PURPOSE: To investigate the feasibility of assessing, noninvasively, aortic pulse pressure (APP) and pulse wave velocity (PWV) in the ascending aorta of young adults by means of velocity-encoded magnetic resonance (MR) imaging. MATERIALS AND METHODS: In a series of 11 healthy volunteers, velocity-encoded MR imaging provided pairs of magnitude and phase-contrast images. Blood flow velocity and aortic cross-sectional area (CSA) were determined with a 30-msec temporal resolution. A model analysis revealed that variation in aortic CSA and in maximal blood flow velocity throughout systole could be used to estimate APP and, hence, to derive PWV by means of two different methods. RESULTS: Mean +/- SD values of the APP for the series were 54.2 +/- 16.4 mmHg (range 32.2-84.1 mmHg). The ascending aortic PWV mean +/- SD values were 5.03 +/- 1.10 m/second and 5.37 +/- 1.23 m/second according to the two methods, and both estimates were not significantly different (95% confidence level). CONCLUSION: These results are in agreement with previously published data, suggesting that APP and PWV can be determined, noninvasively, in young adults using MRI.

Factors influencing accuracy of CT-guided percutaneous biopsies of pulmonary lesions.

The purpose of this study was to evaluate the performance and complication rate of CT-guided percutaneous lung biopsy of pulmonary lesions using a coaxial automated biopsy device and to determine factors influencing the false negative rate for the diagnosis of malignancy. A prospective study of 605 consecutive biopsies performed in 595 patients was undertaken. The performances for the diagnosis of malignancy, for the specific diagnosis of benignity and the complication rate were calculated. Patients' characteristics and lesion and procedure variables were included in a logistic regression model and analyzed as potential predictive variables for occurrence of a false-negative diagnosis of malignancy. The sensitivity, specificity, positive predictive value and negative predictive value for a diagnosis of malignancy were 92.2, 99.1, 99.8 and 73.3%, respectively. A specific diagnosis of benignity was obtained in 43 cases (40%) biopsies. The pneumothorax rate was 17.4% (n = 105) with 3 (0.5%) requiring drainage. At multivariate analysis, the sole variable significantly associated with a higher rate of false negative diagnosis of malignancy was lesion size equal to or smaller than 10 mm in diameter. Using a coaxial automated device, CT-guided percutaneous biopsy of pulmonary lesions of size equal to or less than 10 mm in diameter provides a high diagnostic yield with an acceptable complication rate.

Quantitative MRI comparison of systemic hemodynamics in Mustard/Senning repaired patients and healthy volunteers at rest.

The purpose of the present study was to non-invasively compare ascending aortic blood flow and cross-sectional area (CSA) variations vs time in Mustard or Senning repaired (MSR) patients against those of healthy volunteers at rest. Velocity-encoded MR imaging was performed in 10 male patients (age range 18-24 years, median age 20.5 years) late after a Mustard or Senning correction, and in 10 male healthy volunteers (age range 21-25 years, median age 22.5 years), at the upper part of the ascending aorta. Both aortic cross-sectional area (CSA) and blood-flow variations were recorded over a complete cardiac cycle, with a 30-ms time of resolution. The body-surface area (BSA), the mean CSA over the systolic phase, and the BSA-normalized systemic ventricle power and work were significantly lower in the patient series compared with those of the volunteer series. The BSA-normalized right ventricle (RV) power and work of MSR patients were equal to 87 and 83% on average of those of the left ventricle (LV) of healthy volunteers. We conclude that, at rest, the mechanical performance of the systemic RV in MSR patients is significantly lower than that of the LV in healthy volunteers. Furthermore, the significantly lower aortic CSA found in MSR patients than in healthy volunteers may reveal an increase in the vasomotor tone.

Percutaneous biopsy in lung cancer.

This paper presents current indications, contraindications, technical aspects, complications and yield of diagnosis of percutaneous lung biopsy in the setting of lung cancer. Percutaneous lung biopsy should be performed each time that the therapeutic strategy can be significantly influenced, when the procedure is technically feasible and to patients for which the benefits outweigh the risks, that are pneumothorax and pulmonary haemorrhage. Factors identified as potentially favouring post-biopsy pneumothorax are numerous whereas the use of a needle size larger than 18 gauge is the major risk factor of bleeding. Although a coaxial system is highly suitable in any case, two categories of needles can be used; those providing aspiration and those for core biopsies. Both offer similar yields for the diagnosis of malignancy, but core biopsies are more efficient for the specific diagnosis of benignity and lymphoma. Technical improvements of guidance, needle design and pathological techniques may contribute to lower the size limit of the nodule to be biopsied, to decrease the complication rate and their severity and to increase the yield of diagnosis.