Vassilis Koutoulidis

Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: A study of the International Myeloma Working Group

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT. In comparison, WBCT failed to detect some bone destructions in the appendicular skeleton possibly due to limitations of the field of view. Presence of lytic bone lesions in WBCT was of borderline prognostic significance (P=0.051) for SMM patients, with a median time to progression of 38 versus 82 months for those without bone destructions. In conclusion, WBCT identifies significantly more sites of bone destruction than CSS. More than 20% of patients with SMM according to CSS have in fact active MM detectable with WBCT. On the basis of this and other studies, WBCT (either computed tomography (CT) alone or as part of a positron emission tomography-CT protocol) should be considered the current standard for the detection of osteolytic lesions in MM.

Quantitative Diffusion-weighted Imaging of the Bone Marrow: An Adjunct Tool for the Diagnosis of a Diffuse MR Imaging Pattern in Patients with Multiple Myeloma.

Purpose To evaluate the apparent diffusion coefficients (ADCs) of magnetic resonance (MR) imaging patterns in the bone marrow of patients with multiple myeloma (MM) and to determine a threshold ADC that may help distinguish a diffuse from a normal pattern with high accuracy. Materials and Methods This prospective study was approved by the ethics review board, and informed consent was obtained. Ninety-nine patients with newly diagnosed, untreated MM and 16 healthy control subjects underwent spinal MR imaging including diffusion-weighted imaging, and bone marrow ADCs were calculated. Pattern assignment was based on visual assessment of conventional MR images. The Kruskal-Wallis H test, the Mann-Whitney test, and the one-way analysis of variance were used to compare ADCs between patient subsets and control subjects, and a receiver operating characteristic analysis was performed. Results Mean ADCs ± standard deviation in patients with MM for the normal, focal, and diffuse MR imaging patterns were 0.360 × 10-3 mm2/sec ± 0.110, 1.046 × 10-3 mm2/sec ± 0.232, and 0.770 × 10-3 mm2/sec ± 0.135, respectively. There were significant differences in ADCs between diffuse and normal (P < .001), diffuse and focal (P < .001), and focal and normal (P < .001) patterns. Patients with a diffuse pattern had more features of advanced disease, higher international staging system score, increased incidence of high-risk cytogenetics, and higher revised international staging system score. ADCs greater than 0.548 × 10-3 mm2/sec showed 100% sensitivity (26 of 26) and 98% specificity (48 of 49) for the diagnosis of a diffuse (vs normal) MR imaging pattern, whereas an ADC greater than 0.597 × 10-3 mm2/sec showed 96% sensitivity (25 of 26) and 100% specificity (49 of 49). Conclusion ADCs of MR imaging patterns in patients with MM differ significantly. A diffuse MR imaging pattern can be distinguished more objectively from a normal MR imaging pattern by adding quantitative diffusion-weighted imaging to standard MR imaging protocols.

Incremental prognostic value of MRI in the staging of early cervical cancer: a prospective study and review of the literature.

This is to evaluate the predictive ability of clinical examination and preoperative magnetic resonance imaging (MRI) for the staging of early cervical cancer. We prospectively evaluated 115 patients with cervical cancer, International Federation of Gynecologic and Obstetrics (FIGO) stage <IIB; receiver operating characteristic (ROC) analysis determined the predictive ability of MRI, clinical assessment, and their combination for tumor staging. Surgery was the standard of reference. MRI was more accurate than clinical examination for tumor estimate, parametrial or internal os involvement. When combined with MRI, the predictive ability of clinical examination for overall staging [area under the curve (AUC)=0.59, P>.05) increased significantly (AUC=0.84, P<.05). Our results support the official incorporation of MRI into FIGO classification system.

Functional and molecular MRI of the bone marrow in multiple myeloma

MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as diffusion-weighted imaging (spinal or whole body), intravoxel incoherent motion, and dynamic contrast enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma. These non-invasive functional techniques are also being evaluated as imaging biomarkers for response assessment in myeloma patients. The purpose of this article is to provide a comprehensive critical review on the current use and potential future applications of these advanced MRI techniques in multiple myeloma. In addition, we will address the technologies involved and describe the qualitative and quantitative characteristics of normal bone marrow with these techniques.

Lymphomas: The Role of CT and MRI in Staging and Restaging

Lymphoma is a heterogeneous group of more than 30 distinct types, differing widely in epidemiology and clinical behavior. Once the pathologic diagnosis of lymphoma is established, accurate clinical staging is mandatory for prognostication and appropriate treatment planning. In practically all cases, imaging—anatomic cross sectional imaging (CT and/or MRI) and/or functional imaging (PET or PET/CT)—plays a central role in staging. Furthermore, imaging is used to restage during therapy or at the end of treatment and document or exclude a complete remission. The following chapter examines the role of CT and MRI in lymphoma staging and restaging. Advantages and drawbacks of CT in assessing nodal and extranodal disease at initial presentation are discussed, and its diagnostic value compared with PET/CT is presented. The use of CT in restaging, including its role in the revised 2007 International Harmonization Project response criteria is also addressed. The role of MRI in staging and restaging Primary CNS Lymphoma and the use of Whole-body MRI as an alternative radiation-free imaging modality for lymphoma assessment are discussed in the final section of the chapter.

A novel metal-based imaging probe for targeted dual-modality SPECT/MR imaging of angiogenesis

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.

MR imaging features and tumor biomarkers of screen-detected and non-screen detected breast cancers: preliminary results of a comparative study

PURPOSE To investigate differences in clinical features, MRI findings and tumor biomarker characteristics in screen-detected (SCD) and non-screendetected (NSCD) cancers. MATERIAL AND METHODS A total of 62 women (mean age, 48.4 years; range, 33-68 years) with biopsy confirmed breast cancer who underwent preoperative breast MRI were retrospectively evaluated by two expert radiologists. The women were divided into two groups according to the mode of cancer detection (Group A: screen- detected, Group B: non-screen/symptomatic cancer) and clinical, histopathological, MRI characteristics and biomarker features in each group were evaluated. RESULTS NSCD tumors had significantly greater size (3.5 cm vs. 2.1 cm) and Ki-67 expression (68.4% vs. 41.7%) in comparison to SCD cancers. NSCD cancers were less likely to have strongly positive progesterone receptors (Pr) and more likely to have Ki-67 > 15% or positive nodal status (47.4% vs. 8.3%). Increased breast density (ACR C and D: 78.9% vs. 50%ACR A and B) and intense background parenchymal enhancement (BPE, moderate/marked: 42.1% vs. 8.3% minimal/mild) were significantly more frequent in NSCD cases. CONCLUSION NSCD cancers had higher prevalence of poor prognostic characteristics in comparison to SCD tumors, including larger tumor size, higher Ki-67 index, and positive nodes. Increased fibroglandular tissue and intense BPE were both strongly associated with NSCD cancers, supporting their use as potential MR biomarkers in breast cancer risk models.

Recommendations for acquisition, interpretation and reporting of whole body low dose CT in patients with multiple myeloma and other plasma cell disorders: a report of the IMWG Bone Working Group

Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders.

Anatomic Classification of Lymph Nodes

One of the most widely used, imaging-based classifications of cervical lymph nodes (LNs) is the one introduced by Som et al., which is based on the clinical classifications of the American Joint Committee on Cancer and the American Academy of Otolaryngology-Head and Neck Surgery [1–3]. This classification system has been shown to be simple and consistent, with nodal levels easily distinguished by radiologists on axial slices of neck CT and MRI exams. Although this system was originally conceived as a nodal mapping guide for selecting the most appropriate neck dissection procedure, its simplicity and reproducibility make it appropriate for other clinical uses, including assessment of lymphoma patients. Indeed, in the case of lymphoma, standardization of lymph node terminology facilitates communication between imagers (radiologists and nuclear physicians) and clinicians (oncologists, hematologists, and radiotherapists) and aids correct evaluation of initial disease extent, treatment planning, and treatment response assessment.

The Abnormal Bone Marrow: MRI Patterns

The signal intensity of bone marrow on MR images depends on the balance among fat, water, and bony trabeculae. Normal patterns of red to yellow marrow conversion in relation to age and gender and variations in these patterns depending on daily habits (e.g., smoking, long-distance running), chronic illnesses (e.g., severe anemia), and body habitus (obesity), via the process of reconversion, have already been discussed in Chap. 1. In this chapter, the MRI patterns of the abnormal bone marrow will be analyzed. When dealing with MR images of bone marrow disorders, pattern recognition is an essential step of the diagnostic process. Analysis of the MR pattern of involvement permits a classification of marrow disorders which is based on imaging findings rather than on clinical or laboratory information; it narrows down the differential diagnosis and aids distinction of a “leave alone” finding from one that needs follow-up or further work-up. Pattern assignment may also have important clinical implications regarding prognosis in certain conditions, such as multiple myeloma, as will be discussed in the relevant chapters [1].