Predicting cytogenetic risk in multiple myeloma using conventional whole-body MRI, spinal dynamic contrast-enhanced MRI, and spinal diffusion-weighted imaging.

OBJECTIVES: Cytogenetic abnormalities are predictors of poor prognosis in multiple myeloma (MM). This paper aims to build and validate a multiparametric conventional and functional whole-body MRI-based prediction model for cytogenetic risk classification in newly diagnosed MM. METHODS: Patients with newly diagnosed MM who underwent multiparametric conventional whole-body MRI, spinal dynamic contrast-enhanced (DCE-)MRI, spinal diffusion-weighted MRI (DWI) and had genetic analysis were retrospectively included (2011-2020/Ghent University Hospital/Belgium). Patients were stratified into standard versus intermediate/high cytogenetic risk groups. After segmentation, 303 MRI features were extracted. Univariate and model-based methods were evaluated for feature and model selection. Testing was performed using receiver operating characteristic (ROC) and precision-recall curves. Models comparing the performance for genetic risk classification of the entire MRI protocol and of all MRI sequences separately were evaluated, including all features. Four final models, including only the top three most predictive features, were evaluated. RESULTS: Thirty-one patients were enrolled (mean age 66 ± 7 years, 15 men, 13 intermediate-/high-risk genetics). None of the univariate models and none of the models with all features included achieved good performance. The best performing model with only the three most predictive features and including all MRI sequences reached a ROC-area-under-the-curve of 0.80 and precision-recall-area-under-the-curve of 0.79. The highest statistical performance was reached when all three MRI sequences were combined (conventional whole-body MRI + DCE-MRI + DWI). Conventional MRI always outperformed the other sequences. DCE-MRI always outperformed DWI, except for specificity. CONCLUSIONS: A multiparametric MRI-based model has a better performance in the noninvasive prediction of high-risk cytogenetics in newly diagnosed MM than conventional MRI alone. CRITICAL RELEVANCE STATEMENT: An elaborate multiparametric MRI-based model performs better than conventional MRI alone for the noninvasive prediction of high-risk cytogenetics in newly diagnosed multiple myeloma; this opens opportunities to assess genetic heterogeneity thus overcoming sampling bias. KEY POINTS: • Standard genetic techniques in multiple myeloma patients suffer from sampling bias due to tumoral heterogeneity. • Multiparametric MRI noninvasively predicts genetic risk in multiple myeloma. • Combined conventional anatomical MRI, DCE-MRI, and DWI had the highest statistical performance to predict genetic risk. • Conventional MRI alone always outperformed DCE-MRI and DWI separately to predict genetic risk. DCE-MRI alone always outperformed DWI separately, except for the parameter specificity to predict genetic risk. • This multiparametric MRI-based genetic risk prediction model opens opportunities to noninvasively assess genetic heterogeneity thereby overcoming sampling bias in predicting genetic risk in multiple myeloma.

Review of diffusion-weighted imaging and dynamic contrast-enhanced MRI for multiple myeloma and its precursors (monoclonal gammopathy of undetermined significance and smouldering myeloma).

The last decades, increasing research has been conducted on dynamic contrast-enhanced and diffusion-weighted MRI techniques in multiple myeloma and its precursors. Apart from anatomical sequences which are prone to interpretation errors due to anatomical variants, other pathologies and subjective evaluation of signal intensities, dynamic contrast-enhanced and diffusion-weighted MRI provide additional information on microenvironmental changes in bone marrow and are helpful in the diagnosis, staging and follow-up of plasma cell dyscrasias. Diffusion-weighted imaging provides information on diffusion (restriction) of water molecules in bone marrow and in malignant infiltration. Qualitative evaluation by visually assessing images with different diffusion sensitising gradients and quantitative evaluation of the apparent diffusion coefficient are studied extensively. Dynamic contrast-enhanced imaging provides information on bone marrow vascularisation, perfusion, capillary resistance, vascular permeability and interstitial space, which are systematically altered in different disease stages and can be evaluated in a qualitative and a (semi-)quantitative manner. Both diffusion restriction and abnormal dynamic contrast-enhanced MRI parameters are early biomarkers of malignancy or disease progression in focal lesions or in regions with diffuse abnormal signal intensities. The added value for both techniques lies in better detection and/or characterisation of abnormal bone marrow otherwise missed or misdiagnosed on anatomical MRI sequences. Increased detection rates of focal lesions or diffuse bone marrow infiltration upstage patients to higher disease stages, provide earlier access to therapy and slower disease progression and allow closer monitoring of high-risk patients. Despite promising results, variations in imaging protocols, scanner types and post-processing methods are large, thus hampering universal applicability and reproducibility of quantitative imaging parameters. The myeloma response assessment and diagnosis system and the international myeloma working group provide a systematic multicentre approach on imaging and propose which parameters to use in multiple myeloma and its precursors in an attempt to overcome the pitfalls of dynamic contrast-enhanced and diffusion-weighted imaging.Single sentence summary statementDiffusion-weighted imaging and dynamic contrast-enhanced MRI provide important additional information to standard anatomical MRI techniques for diagnosis, staging and follow-up of patients with plasma cell dyscrasias, although some precautions should be taken on standardisation of imaging protocols to improve reproducibility and application in multiple centres.

Susac syndrome complicating a SARS-CoV-2 infection.

In 2020 the world was captivated by the COVID-19 pandemic. Current scientific evidence suggests an interaction of SARS-CoV-2 and the human immune system. Multiple cases were reported of patients with COVID-19 presenting with encephalopathy, confusion or agitation, stroke, and other neurologic symptoms. We present a case of a 40-year-old man diagnosed with Susac syndrome after COVID-19, presenting with acute sensorineural hearing loss, encephalopathy, a splenial "snowball-like" lesion, and branch retinal artery occlusions with distal arterial wall hyperintensity. Although the pathophysiology of Susac syndrome remains unclear, this case is in line with the ongoing debate about the influence of SARS-CoV-2 on the human immune system. Corticosteroid treatment was initiated, followed by two treatments with rituximab, with clinical improvement of the symptomatology. Maintenance treatment currently consists of mycophenolic acid (MPA). Future research will need to focus on the underlying mechanisms for COVID-19-associated (autoimmune) complications.

Delayed Post-Anoxic White Matter Injury in an Infant.

Teaching Point: White matter reversal on diffusion-weighted magnetic resonance imaging is indicative of delayed post-anoxic encephalopathy. This manifests sooner in young infants than in adults.

Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma.

Magnetic resonance imaging (MRI) is the most sensitive imaging technique for the detection of bone marrow infiltration, and has therefore recently been included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. Nevertheless, conventional MRI only provides anatomical information and is therefore only of limited use in the response assessment of patients with multiple myeloma. The additional information from functional MRI techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, can improve the detection rate of bone marrow infiltration and the assessment of response. This can further enhance the sensitivity and specificity of MRI in the staging of multiple myeloma patients. This article provides an overview of the technical aspects of conventional and functional MRI techniques with practical recommendations. It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages.

MRI in multiple myeloma: a pictorial review of diagnostic and post-treatment findings.

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity.This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message • Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. • Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. • Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. • Combined morphological and functional MRI provides optimal bone marrow assessment for staging. • Combined morphological and functional MRI is of considerable value in treatment follow-up.

Combined evaluation of conventional MRI, dynamic contrast-enhanced MRI and diffusion weighted imaging for response evaluation of patients with multiple myeloma.

PURPOSE: To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group (IMWG) response criteria. MATERIALS AND METHODS: The retrospective study includes 27 newly diagnosed patients, providing 99 MRI-investigations. Patients were categorized according to the IMWG response criteria. Quantitative assessment was based on signal intensities (SI) of T1-weighted, fat-saturated T2-weighted and b1000 images, apparent diffusion coefficients (ADC) and parameters from time-intensity-curves (TIC) derived from L3. Qualitative visual analysis of conventional MRI-images, b1000-images and TICs, providing a "combined skeletal score", was used to create MRI response criteria. RESULTS: The combined skeletal score could significantly differentiate between subgroups based on IMWG response criteria (p=0.016). The gold standard plasmacytosis could significantly differentiate between subgroups based on MRI response criteria (p<0.001), as well as slope (p<0.001) and ADC (p=0.006). There is a good agreement between IMWG and MRI response criteria (Kendall's coefficient=0.761). CONCLUSION: Response evaluation of MM-patients based on the combination of anatomical information from conventional MRI with functional information from DCE-MRI and DWI, is useful for monitoring therapy.

The diagnostic value of SE MRI and DWI of the spine in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma.

OBJECTIVES: To evaluate DWI of the bone marrow in the differentiation of monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma (SMM) and multiple myeloma (MM). METHODS: The retrospective study includes 64 patients with MGUS, 27 with SMM, 64 with new MM and 12 controls. Signal intensity (SI) of spinal SE-MRI and DWI (b0-1000) as well as apparent diffusion coefficients (ADC) were measured in the T10 and L3. Qualitative assessment of b-images was performed by one experienced radiologist. RESULTS: ADC600 and ADC1000 are the best ADC values in differentiating patient groups (p < 0.030). SIT2, SIb1000 and ADC1000 are higher and SIT1 lower in L3 compared to T10 (p < 0.050). All quantitative parameters of L3 can differentiate significantly between MGUS and MM (p < 0.050) and between patients with percentage plasma cells (PC%) between 0-10 % compared to >50 % (p = 0.001). Only SIT2 for L3 can differentiate MGUS from SMM (p = 0.044) and PC%0-10 from PC%10-25 (p = 0.033). Qualitative interpretation of b1000 images allows differentiating MM patients from those with MGUS or SMM (p < 0.001). CONCLUSIONS: Spinal SE-MRI can differentiate among MGUS, SMM, MM and control subjects. DWI based on the SI on b1000 images and ADC values is increased in MM compared to MGUS and SMM. Qualitative assessment of b-images can differentiate MM from MGUS or SMM. KEY POINTS: • ADC values are higher in patients with MM compared to MGUS • DWI parameters change late in disease evolution • DWI is sensitive but not specific in diagnosing patients with MM • Qualitative DWI assessment is good in detecting myeloma patients.

Value of whole body MRI and dynamic contrast enhanced MRI in the diagnosis, follow-up and evaluation of disease activity and extent in multiple myeloma.

PURPOSE: To evaluate the significance of dynamic contrast enhanced MRI (DCE-MRI) and whole body MRI (WB-MRI) in the diagnosis, prognosis and assessment of therapy for patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). MATERIALS AND METHODS: The retrospective study includes 219 patients providing 463 WB-MRI and DCE-MRI investigations for the subgroups MGUS (n=70), MM active disease (n=126; this includes 70 patients with new diagnosis of MM, according to the International Staging System (ISS): 41.4% ISS stage I, 20.0% ISS stage II, 7.1% ISS stage III, 31.4% insufficient for staging; and 56 patients with '(re-)active disease': 16.07% relapse, 32.14% progressive disease and 51.79% stable disease) and MM remission (n=23; 60.87% complete remission, 17.39% very good partial remission and 21.74% partial remission). Investigations of patients with hereditary multiple exostoses (n=5), neurofibromatosis (n=7) and healthy persons (n=9) were added as control subjects (n=21). WB-MRI evaluation was done by evaluating thirteen skeletal regions, providing a 'skeletal score'. DCE-MRI images of the spine, were analyzed with regions-of-interest and time-intensity-curves (TIC). RESULTS: All TIC parameters can significantly differentiate between the predefined subgroups (p<0.001). One hundred days after autologous stem cell transplantation a 75% decrease of the slope wash-in value (p<0.001) can be seen. A cubic regression trend between 'skeletal score' and slope wash-in (adj.R(2)=0.412) could demonstrate a significant increase bone marrow perfusion if MM affects more than 10 skeletal regions (p<0.001), associated with a poorer prognosis (p<0.001). CONCLUSION: DCE-MRI evaluation of the spine is useful for diagnosis of MM, follow-up after stem cell transplantation and evaluation of disease activity. A combined evaluation with WB-MRI and DCE-MRI provides additional micro-vascular information on the morphologic lesions and could help categorize patients with MM in two different groups to offer useful therapeutic and prognostic advise.