Alberto Bazzocchi

Integrated Imaging Approach to Osteoporosis: State-of-the-Art Review and Update

Osteoporosis is the most common of all metabolic bone disorders. It is characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fractures. Because of the increasing aging of the world population, the number of persons affected by osteoporosis is also increasing. Complications related to osteoporosis can create social and economic burdens. For these reasons, the early diagnosis of osteoporosis is crucial. Conventional radiography allows qualitative and semiquantitative evaluation of osteoporosis, whereas other imaging techniques allow quantification of bone loss (eg, dual-energy x-ray absorptiometry and quantitative computed tomography [CT]), assessment for the presence of fractures (morphometry), and the study of bone properties (ultrasonography). In recent years, new imaging modalities such as micro-CT and high-resolution magnetic resonance imaging have been developed in an attempt to help diagnose osteoporosis in its early stages, thereby reducing social and economic costs and preventing patient suffering. The correct diagnosis of osteoporosis results in better management in terms of prevention and adequate pharmacologic or surgical treatment.

Accuracy, reproducibility and repeatability of ultrasonography in the assessment of abdominal adiposity.

RATIONALE AND OBJECTIVES Despite improvements in the methods used in body composition analysis, some goals remain far from clinical practice. Among them, the most important is the quantification of intra-abdominal adipose tissue. Fat distribution is a key point in the assessment of cardiovascular and metabolic risk status. The aim of this study was to define the accuracy, reproducibility, and repeatability of ultrasonography in the evaluation of abdominal adiposity. MATERIALS AND METHODS Twenty-six nonobese patients (group A) who underwent computed tomographic (CT) abdominal imaging and 29 obese patients (group B) were enrolled. Patients from both groups were independently evaluated using ultrasound by three radiologists; computed tomography-like conditions were reproduced, and six main parameters of subcutaneous and internal adiposity were measured (as well as three derived indexes) with both linear and convex probes. In group A, the same measurements were also obtained on CT images. Time spent for every ultrasound session was recorded. Results were analyzed using Lins concordance correlation (ρ), intraclass correlation, and linear regression analysis (and analysis of variance). RESULTS Three patients were excluded from group A after CT scans because of technical problems. Mesenteric fat thickness did not show significant correlations and reliability. Strong correlations between ultrasound and CT measurements were observed for all other visceral and subcutaneous parameters (ρ = 0.85-0.96). Intraobserver and interobserver agreement was excellent in both groups (repeatability: ρ = 0.83-0.99 for group A, ρ = 0.90-0.99 for group B; reproducibility: intraclass correlation coefficient = 0.90-0.99 for groups A and B). The mean time spent was 95 ± 21 seconds for group A (mean body mass index, 27.4 ± 2.4 kg/m(2)) and 129 ± 33 seconds for group B (mean body mass index, 37.3 ± 11.9 kg/m(2)). CONCLUSIONS Ultrasound is accurate, reproducible, and fast in the analysis of abdominal adiposity. It offers a regional, easy, and close-at-hand evaluation of subcutaneous and visceral fat compartments. This should be taken into consideration when clinical routine examinations are performed or to evaluate patients with specific metabolic diseases before and after treatment.

Mr-guided Focused Ultrasound (mrgfus) Ablation for the Treatment of Nonspinal Osteoid Osteoma: A Prospective Multicenter Evaluation

BACKGROUND Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel imaging-guided surgical technique that allows the performance of noninvasive and radiation-free ablation. Presently, computed tomography (CT)-guided radiofrequency ablation, a minimally invasive percutaneous technique, is the standard for treating symptomatic osteoid osteomas. The purpose of this study was to evaluate the use of MRgFUS ablation for the treatment of nonspinal osteoid osteomas in terms of technical success, complications, and clinical success through one year of follow-up. METHODS In this prospective multicenter study, thirty consecutive patients with a nonspinal osteoid osteoma were enrolled between May 2010 and April 2012 at three different university centers; twenty-nine of the patients were treated with use of MRgFUS. Lesions had been previously diagnosed on the basis of imaging, including dynamic contrast-enhanced MR. The mean number of sonications and energy deposition were determined. Technical success was evaluated through an assessment of complications immediately after treatment. Clinical success was determined on the basis of pain reduction as measured with a visual analog scale (VAS), recurrence, and long-term complications through twelve months. RESULTS Technical success of MRgFUS was observed for all twenty-nine patients. The mean number of sonications (and standard deviation) was 7 ± 3, and the mean delivered acoustic energy was 1180 ± 736 J. At the twelve-month follow-up, complete clinical success was observed in twenty-six (90%) of the twenty-nine patients (95% confidence interval [CI] = 84 to 95; mean VAS, 0 ± 0 points). Partial success was observed in three (10%) of the twenty-nine patients (95% CI = 5 to 16; mean VAS score, 5 ± 0 points); two of these patients subsequently underwent CT-guided radiofrequency ablation, and one underwent open surgery. Pain score values showed a significant reduction (p < 0.001) between baseline (mean VAS score, 8 ± 1 points) and post treatment (mean VAS score, 1 ± 2 points). No complications were observed. CONCLUSIONS MRgFUS may be an effective and safe alternative approach in the treatment of nonspinal osteoid osteoma. A complete clinical success rate of 90% was demonstrated without adverse events. MRgFUS is totally noninvasive and eliminates radiation exposure.

Contrast enhanced MRI and 18F-FDG PET-CT in the assessment of multiple myeloma: A comparison of results in different phases of the disease

OBJECTIVES The aim of our study was to compare the accuracy of contrast enhanced MRI and FDG PET-CT in the staging, treatment evaluation and follow-up of multiple myeloma. METHODS We retrospectively reviewed 210 PET-CT and 210 MRI studies of patients affected by multiple myeloma. MRI was always performed within 15 days of PET-CT. All the images have been evaluated by two expert oncologic radiologists. RESULTS Patient population included 81 females and 110 males (age 61.9 ± 9.9 years-old). Sixty-two patients have been evaluated at diagnosis, 58 at the end of therapies and 90 during follow-up. In 12/62 patients (19.4%) at diagnosis, differences between MRI and PET-CT findings determined changes in the staging: PET-CT was responsible for 11 down-staging (17.7%) and MRI only for one (1.6%). In 27/40 patients (67.5%) with good or complete clinical response to therapies the normalization of findings was faster for PET-CT than MRI. Ten out of 90 patients (10/90 - 11.1%) in follow-up protocol presented clinical recurrence of the disease: MRI detected active lesions in 8 of them (80.0%) and PET-CT in 5 patients (50.0%, all detected by MRI too). CONCLUSIONS MRI achieved better results than PET-CT in the staging and in patients with multiple myeloma recurrence. PET-CT, showed prompt change of imaging findings, faster than MRI, in patients with positive response to therapy.

Computed Tomographic Pulmonary Angiography for Diagnosis of Invasive Mold Diseases in Patients With Hematological Malignancies

BACKGROUND Invasive mold diseases (IMDs) of the lung remain a challenge for immunocompromised patients. Although timely diagnosis and treatment are crucial for the outcome of the infection, the poor sensitivity of microbiological techniques and the limited specificity of chest high-resolution computed tomography (HRCT) often delay definitive diagnosis of these infections. METHODS To explore the diagnostic utility of computed tomographic pulmonary angiography (CTPA) for detecting angioinvasive patterns of pulmonary infection, we performed a single-center, prospective, nonrandomized trial involving 36 patients with hematological malignancies who had clinical suspicion of IMD, as defined by European Organization for Research and Treatment of Cancer/Mycosis Study Group diagnostic criteria. RESULTS We found that 5 of 5 patients with proven IMD had CTPA-positive findings consistent with interruption of the arterial vessels (concordance, 100%). CTPA findings were positive in 5 of 7 patients with probable IMD (findings for 2 were considered false negative because lesions were too small or not evaluable). In 15 of 24 patients with a final diagnosis of possible IMD, CTPA findings were negative for 14 patients and were positive for 1 patient, who had septic emboli associated with Staphylococcus aureus bacteremia. CTPA findings were positive in the remaining 9 patients with a final diagnosis of possible IMD at the end of the study. CONCLUSIONS We conclude that CTPA appears to be a promising tool to exclude the diagnosis of IMD in high-risk patients without specific findings on HRCT scans, and it is most useful in the presence of well-circumscribed lesions in which there is suspicion for IMD.

Effects of Three Different Testosterone Formulations in Female-to-Male Transsexual Persons

INTRODUCTION Gender dysphoria is characterized by a strong discomfort with the gender assigned at birth and the urge to live as a member of the opposite gender. The acquisition of phenotypic features of the desired gender requires the use of cross-sex hormones. Female-to-male (FtM) transsexual persons are treated with testosterone to induce virilization. AIM The aim of the study was to assess the effects of three different testosterone formulations on body weight and composition and metabolic and bone parameters. METHODS Forty-five FtM transsexuals were randomly assigned to receive testoviron depot (i.m.: 100 mg/10 days; n = 15), testosterone gel (50 mg/die; n = 15), and testosterone undecanoate (i.m.: 1,000 mg every 6 weeks for the first 6 weeks and then every 12 weeks, n = 15). FtM individuals were studied before, at week 30, and at week 54 of testosterone treatment. MAIN OUTCOME MEASURES Anthropometric, metabolic, bone, hematological, and biochemical parameters were evaluated at baseline and after 12 months of treatment. RESULTS Lean body mass significantly increased and fat mass decreased in all groups. No modifications were reported in fasting insulin and insulin sensitivity index. High-density plasma lipoprotein levels declined significantly and low-density lipoprotein concentrations increased significantly in the three groups. The activated partial thromboplastin time and factor I did not change while prothrombin time significantly increased in all groups. At week 54, all subjects were amenorrheic and time to amenorrhea did not differ between the three groups. Current general life satisfaction was increased in all subjects after 1 year of treatment. CONCLUSIONS One-year testosterone administration in FtM transsexuals appears to be very safe with no differences among the testosterone formulations used. Our study is preliminary, and the detection of subtle or long-term differences in the effects of the three formulations may require further larger and longer term studies in this and other populations.

Health and ageing: A cross-sectional study of body composition

BACKGROUND & AIMS The aim of this work was to provide a complete profile of body composition (BC) in healthy subjects and to investigate age and gender-related differences by dual-energy X-ray absorptiometry (DXA) and its latest developments. METHODS Italian volunteers among blood donors were enrolled in 5 different age bands (from 18 to 70 years old) to reach the threshold of 25 males and 25 females per single band (total: 250 subjects). All non-obese subjects who satisfied selective inclusion criteria were measured for weight and height and submitted to DXA, to determine fat mass (FM), non-bone lean mass (LM), bone mineral content and density, at regional and whole-body level. Moreover, the assessment of android visceral FM was performed by a new software. RESULTS A decrease in LM and increase in FM was observed with ageing, although the phenomenon was proved to be attenuated in women. The central and visceral redistribution of FM was also shown along lifetime, but women were not affected as men by this change. CONCLUSIONS This paper is a report on the status of healthy Italian subjects in their adulthood, to be used as a reference for future investigations on physiology, pathological human conditions, and differences between countries.

Relationship between body composition, body mass index and bone mineral density in a large population of normal, osteopenic and osteoporotic women.

PurposeThe knowledge of factors modulating the behaviour of bone mass is crucial for preventing and treating osteoporotic disease; among these factors, body weight (BW) has been shown to be of primary importance in postmenopausal women. Nevertheless, the relative effects of body composition indices are still being debated. Our aim was to analyze the relationship between body mass index (BMI), fat and lean mass and bone mineral density (BMD) in a large population of women. Moreover, this study represents a first important report on reference standard values for body composition in Italian women.Materials and methodsBetween 2005 and 2008, weight and height of 6,249 Italian women (aged 30–80 years) were measured and BMI was calculated; furthermore BMD, bone mineral content, fat and lean mass were measured by dual-energy X-ray absorptiometry. Individuals were divided into five groups by decades (group 1, 30.0–39.9; group 2, 40.0–49.9; group 3, 50.0–59.9; group 4, 60.0–69.9; group 5, 70.0–79.9). Differences among decades for all variables were calculated using a one-way analysis of variance (ANOVA) and Bonferroni test by the SPSS programme.ResultsMean BW was 66.8±12.1 kg, mean height 159.1±6.3 cm and mean BMI 26.4±4.7 kg/m2. According to BW and BMI, there was an increase of obesity with age, especially in women older than 50 years (p<0.001). Lean mass increased until 50 years of age but significantly decreased after this age (p<0.001). The percentage of osteopenia and osteoporosis in the examined population was 43.0% and 16.7%, respectively.ConclusionsOur data show that obesity significantly decreased the risk for osteoporosis but did not decrease the risk for osteopenia. It is strongly recommended that a strong policy regarding prevention of osteopenia and osteoporosis be commenced. An overall examination of our results suggests that both fat and lean body mass can influence bone mass and that their relative effect on bone could be modulated by their absolute amount and ratio to total BW.RiassuntoObiettivoLa conoscenza dei fattori che modulano il comportamento della massa ossea è cruciale nella prevenzione e nel trattamento della malattia osteoporotica; tra questi fattori, il peso corporeo (BW) ha dimostrato di essere di primaria importanza nelle donne in postmenopausa. Tuttavia gli effetti relativi degli indici di composizione corporea sono oggi ancora dibattuti. Il nostro obiettivo è stato quello di analizzare la relazione tra l’indice di massa corporea (BMI), la massa grassa, la massa magra e la densità minerale ossea (BMD) in una vasta popolazione di donne. Inoltre questo studio rappresenta un primo importante report sui valori di riferimento standard di composizione corporea nella popolazione femminile italiana.Materiali e metodiNel periodo compreso tra il 2005 e il 2008 sono stati rilevati peso e altezza di 6249 donne italiane (età 40–80 anni), ed è stato calcolato il BMI; inoltre sono stati misurati BMD, contenuto minerale osseo, massa grassa e massa magra attraverso assorbimetria a raggi X a doppia energia. La popolazione dello studio è stata ripartita in 5 gruppi per decade di età (gruppo 1 da 30,0 a 39,9; gruppo 2 da 40,0 a 49,9; gruppo 3 da 50,0 a 59,9; gruppo 4 da 60,0 a 69,9; gruppo 5 da 70,0 a 79,9). Per tutte le variabili sono state calcolate le differenze e la loro significatività tra le decadi di età attraverso l’analisi della varianza a una via (ANOVA) e il test di Bonferroni, utilizzando il software SPSS.RisultatiIl BW medio è stato 66,8±12,1 kg, l’altezza media 159,1±6,3 cm, e il BMI medio 26,4±4,7 kg/ m2. Con l’aumento del BW e del BMI si è osservato un aumento dell’obesità con l’età, soprattutto sopra i 50 anni (p<0,001). La massa magra ha dimostrato di aumentare fino ai 50 anni ma è significativamente diminuita dopo questa età (p<0,001). La percentuale di osteopenia e osteoporosi nell’intera popolazione è stata rispettivamente del 43,0% e 16,7%.ConclusioniI nostri dati hanno mostrato che l’obesità diminuisce il rischio di osteoporosi ma non diminuisce il rischio di osteopenia. È fortemente raccomandato iniziare una rigorosa politica di prevenzione dell’osteopenia e dell’osteoporosi. Un’analisi generale dei nostri risultati suggerisce quindi che sia la massa grassa sia la massa magra possono influenzare la massa ossea e che gli effetti relativi sull’osso possono essere modulati dalla loro quantità assoluta e dal rapporto sul peso corporeo complessivo.

High Resolution Computed Tomography Angiography Improves the Radiographic Diagnosis of Invasive Mold Disease in Patients With Hematological Malignancies

BACKGROUND Computed tomography pulmonary angiography (CTPA) may improve the diagnostic capabilities of CT imaging for invasive mold disease, but its performance relative to other signs (ie, halo sign, hypodense sign, pleural effusion, reversed halo sign) is unknown. METHODS We prospectively compared the diagnostic performance of CTPA vs other CT imaging findings in 100 patients with hematological malignancies and possible invasive mold disease defined by EORTC/MSG criteria. After undergoing extensive diagnostic work-up, patients were upgraded to probable or proven mold disease based on galactomannan antigen, culture or histology; or remained as possible mold disease if an alternative diagnosis could not be established. RESULTS In total, 46 /100 patients who underwent CTPA were upgraded to probable or proven mold disease. Excluding 8 CTPA cases that were nonevaluable by the radiologist, a positive occlusion sign identified by CTPA was 100% sensitive for the diagnosis of probable or proven mold disease (41/41). Among patients who could not be upgraded from the possible mold disease category (n = 51), 25 (49%) had evidence of vessel occlusion by CTPA with only one positive patient eventually reaching an alternative diagnosis (Staphylococcus aureus septic thrombosis). Intravenous and/or oral antifungal therapy was stopped earlier in patients with a negative vs positive CTPA results (P ≤ .001). CONCLUSIONS Vessel occlusion detected by CTPA is a more sensitive and possibly more specific radiographic sign vs other common CT findings of invasive mold disease in patients with hematological malignancies.

DXA: Technical aspects and application.

The key role of dual-energy X-ray absorptiometry (DXA) in the management of metabolic bone diseases is well known. The role of DXA in the study of body composition and in the clinical evaluation of disorders which directly or indirectly involve the whole metabolism as they may induce changes in body mass and fat percentage is less known or less understood. DXA has a range of clinical applications in this field, from assessing associations between adipose or lean mass and the risk of disease to understanding and measuring the effects of pathophysiological processes or therapeutic interventions, in both adult and paediatric human populations as well as in pre-clinical settings. DXA analyses body composition at the molecular level that is basically translated into a clinical model made up of fat mass, non-bone lean mass, and bone mineral content. DXA allows total and regional assessment of the three above-mentioned compartments, usually by a whole-body scan. Since body composition is a hot topic today, manufacturers have steered the development of DXA technology and methodology towards this. New DXA machines have been designed to accommodate heavier and larger patients and to scan wider areas. New strategies, such as half-body assessment, permit accurate body scan and analysis of individuals exceeding scan field limits. Although DXA is a projective imaging technique, new solutions have recently allowed the differential estimate of subcutaneous and intra-abdominal visceral fat. The transition to narrow fan-beam densitometers has led to faster scan times and better resolution; however, inter- or intra-device variation exists depending on several factors. The purposes of this review are: (1) to appreciate the role of DXA in the study of body composition; (2) to understand potential limitations and pitfalls of DXA in the analysis of body composition; (3) to learn about technical elements and methods, and to become familiar with biomarkers in DXA.