Feasibility of bone marrow edema detection using dual-energy cone-beam computed tomography.

BACKGROUND: Dual-energy (DE) detection of bone marrow edema (BME) would be a valuable new diagnostic capability for the emerging orthopedic cone-beam computed tomography (CBCT) systems. However, this imaging task is inherently challenging because of the narrow energy separation between water (edematous fluid) and fat (health yellow marrow), requiring precise artifact correction and dedicated material decomposition approaches. PURPOSE: We investigate the feasibility of BME assessment using kV-switching DE CBCT with a comprehensive CBCT artifact correction framework and a two-stage projection- and image-domain three-material decomposition algorithm. METHODS: DE CBCT projections of quantitative BME phantoms (water containers 100-165 mm in size with inserts presenting various degrees of edema) and an animal cadaver model of BME were acquired on a CBCT test bench emulating the standard wrist imaging configuration of a Multitom Rax twin robotic x-ray system. The slow kV-switching scan protocol involved a 60 kV low energy (LE) beam and a 120 kV high energy (HE) beam switched every 0.5° over a 200° angular span. The DE CBCT data preprocessing and artifact correction framework consisted of (i) projection interpolation onto matched LE and HE projections views, (ii) lag and glare deconvolutions, and (iii) efficient Monte Carlo (MC)-based scatter correction. Virtual non-calcium (VNCa) images for BME detection were then generated by projection-domain decomposition into an Aluminium (Al) and polyethylene basis set (to remove beam hardening) followed by three-material image-domain decomposition into water, Ca, and fat. Feasibility of BME detection was quantified in terms of VNCa image contrast and receiver operating characteristic (ROC) curves. Robustness to object size, position in the field of view (FOV) and beam collimation (varied 20-160 mm) was investigated. RESULTS: The MC-based scatter correction delivered > 69% reduction of cupping artifacts for moderate to wide collimations (> 80 mm beam width), which was essential to achieve accurate DE material decomposition. In a forearm-sized object, a 20% increase in water concentration (edema) of a trabecular bone-mimicking mixture presented as ∼15 HU VNCa contrast using 80-160 mm beam collimations. The variability with respect to object position in the FOV was modest (< 15% coefficient of variation). The areas under the ROC curve were > 0.9. A femur-sized object presented a somewhat more challenging task, resulting in increased sensitivity to object positioning at 160 mm collimation. In animal cadaver specimens, areas of VNCa enhancement consistent with BME were observed in DE CBCT images in regions of MRI-confirmed edema. CONCLUSION: Our results indicate that the proposed artifact correction and material decomposition pipeline can overcome the challenges of scatter and limited spectral separation to achieve relatively accurate and sensitive BME detection in DE CBCT. This study provides an important baseline for clinical translation of musculoskeletal DE CBCT to quantitative, point-of-care bone health assessment.

Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence.

Background: Chronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively. Objective: Our objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association. Method: We recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF). Results: More severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD. Conclusions: The bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.

Functional imaging with dual-energy computed tomography for supplementary non-invasive assessment of mast cell burden in systemic mastocytosis.

Systemic mastocytosis (SM) is characterized by multifocal accumulation of neoplastic mast cells (MCs), predominately affecting the bone marrow (BM). Imaging with computed tomography (CT) is used for assessment of bone mineral density and structure. However, the value of functional imaging with dual-energy CT (DECT) and the assessment of virtual-non-calcium attenuation values (VNCa-AV) for visualization of BM disease burden in SM has not yet been assessed. DECT of the axial skeleton was performed in 18 patients with SM (indolent SM [ISM], n = 6; smoldering SM [SSM]/advanced SM [AdvSM], n = 12) and 18 control subjects. VNCa-AV were obtained in 5 representative vertebraes per patient and correlated with laboratory, morphologic and molecular parameters. VNCa-AV strongly correlated with quantitative BM MC infiltration (r = 0.7, R2 = 0.49, P = 0.001) and serum tryptase levels (r = 0.7, R2 = 0.54, P < 0.001). Mean VNCa-AV were significantly higher in SSM/AdvSM as compared to ISM (- 9HU vs. - 54HU, P < 0.005) and controls (- 38HU, P < 0.005). Nine of 10 (90%) patients with a VNCa-AV > - 30HU and 7/7 (100%) patients with a VNCa-AV > - 10HU had SSM or AdVSM. BM VNCa-AV provide information about the MC burden of SM patients and correlate with SM subtypes. DECT may therefore serve as a supplementary tool for SM diagnosis, subclassification and monitoring in a one-stop-shop session.

Behavior during aging of bone-marrow fatty-acids profile in women's calcaneus to search for early potential osteoporotic biomarkers: a 1H-MR Spectroscopy study.

AIM: Identify new potential biomarkers of osteoporosis at an early stage, by magnetic resonance spectroscopy (MRS), studying early changes in the metabolic profile of bone-marrow fatty acids in women's calcanei during healthy aging and osteoporosis status. METHODS: Single voxel MRS was performed by using a point resolved spectroscopy (PRESS) sequence at 3T. Thirty-four Caucasian women (age range: 22-59 years) were recruited to investigate calcaneus bone marrow. The cohort was constituted of four groups according to age, menopausal status, and T-score evaluated after a DXA examination on the femoral neck. Women were classified in young control (n = 11, mean age = 26.5 ± 3.8 y, age range: 22-34 years), perimenopausal groups (n = 11, mean age = 42.0 ± 3.6 y, age range: 37-47 years), postmenopausal group (n = 9, mean age = 55.4 ± 2.9 y, age range: 50-59 years, mean T-score = -1.70 ± 0.50) and osteoporotic group (n = 6, mean age = 53.0 ± 2.8 y, age range: 50-58 years, mean T-score = -2.54 ± 0.10). The total lipid content (TL), the Unsaturation Index (UI), and the fraction of unsaturated/polyunsaturated fatty acid (fUFA and fPUFA) were calculated. RESULTS: TL was significantly correlated with age (r = 0.73, p < 0.001). TL increases linearly with age in the young + perimenopausal population (r = 0.92, p < 0.001) but this trend is not significant in the postmenopausal subject (r = 0.48, p = 0.07). No significant correlation was found between T-Score and TL in postmenopausal and osteoporotic women, whereas a significant correlation was found between TL and time interval (tp) between the age at menopause and the age of the subject at the MRS examination. Conversely, no correlation was found between T-score and tp. The unsaturation index (UI) does not significantly discriminate between osteoporotic, peri- and postmenopausal women. On the other hand, fUFA is significantly different in peri-menopausal and osteoporotic subjects (p = 0.02), while fPUFA is significantly different both between peri- and postmenopausal women (p = 0.05) and postmenopausal and osteoporotic subjects (p = 0.03). Both fUFA and fPUFA did not correlate with subjects' age. CONCLUSION: In the female calcaneus, fUFA and fPUFA are promising measurable quantities for the characterization of bone marrow's composition potentially correlated with the development of osteoporosis, whereas UI does not differentiate between subjects of varying osteoporotic status. The fact that the TL in the calcaneus is correlated with tp, indicates that active metabolic changes are still occurring in these subjects, giving complementary information to the DXA about the changes in bone marrow's composition which may affect the whole bone health.

Changes in Vertebral Marrow Fat Fraction Using 3D Fat Analysis & Calculation Technique Imaging Sequence in Aromatase Inhibitor-Treated Breast Cancer Women.

Aromatase inhibitor (AI) is a cornerstone drug for postmenopausal women with estrogen receptor-positive early-stage breast cancer. Fat-bone interactions within the bone marrow milieu are growing areas of scientific interest. Although AI treatment could lead to deterioration of the skeleton, the association between AI medication and subsequent marrow adiposity remains elusive. A total of 40 postmenopausal, early-staged, and hormone receptor-positive breast cancer patients who underwent treatment with adjuvant AIs and 40 matched controls were included. Marrow proton density fat fraction (PDFF) at the L1-L4 vertebral bodies using 3D Fat Analysis & Calculation Technique imaging (FACT) sequence at 3.0T, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and serum bone turnover biomarkers were determined at baseline and at 6 and 12 months. We found that, in comparison to baseline, an increase of type I collagen cross-linked telopeptide was detected at 12 months (P <0.05). From baseline to 12 months, the PDFF measured using FACT was greatly increased. At 12 months, the median percent change of PDFF (4.9% vs. 0.9%, P <0.05) was significantly different between the AI treatments and controls. The same trend was observed for the marrow PDFF at 6 months relative to the respective values at baseline. Although BMD values were significantly reduced after 12 months in AI-treated women, changes in BMD vs. baseline condition were not significantly different between the AI-treated and control groups [Δ BMD -1.6% to -1.8% vs. -0.3% to -0.6%, respectively, P > 0.05]. In the AI-treated group, Δ PDFF was associated with Δ BMD at the lumbar spine (r = -0.585, P < 0.001), but not in the controls. Taken together, over a 12-month period, spinal marrow fat content assessed with FACT sequence significantly increased in postmenopausal women with hormone-receptor-positive breast cancer receiving AI treatment.

The role of microscopic bone marrow examination and [123I]MIBG scintigraphy in detection of bone marrow involvement in patients with neuroblastoma.

OBJECTIVES: For the detection of bone marrow (BM) metastases in patients with neuroblastoma, microscopic BM examination and [123I]MIBG scintigraphy are advised. The aims of this study were to assess the concordance of [123I]MIBG and microscopic BM examination (aspirate and biopsy) in detecting BM involvement and to compare invasive disease in BM biopsies and aspirates, both at diagnosis and before autologous stem cell collection (ASCC). METHODS: Fifty-five patients with stage 4 or stage 4S disease were included, and 37 of them received an autologous hematopoietic stem cell transplantation (AHSCT). The concordance rate was measured and paired binary data were analysed by the McNemar test to look for a systematic difference between diagnostic tests. RESULTS: At diagnosis and before ASCC, we found acceptable concordance rates for [123I]MIBG versus microscopic BM examination (77.1% and 85.3% respectively). Discordant results were found in both directions and at both time points. The concordance rate for biopsy versus aspirate at diagnosis was 80.6%, however, before ASCC a much higher concordance rate between both microscopic examinations was found (94.1%). While none of the aspirates showed neuroblastoma cells before ASCC, two biopsies still showed tumor invasion. CONCLUSION: For patients with neuroblastoma, a [123I]MIBG scintigraphy and a microscopic examination of BM aspirate and its biopsy should be used as complementary tools in the evaluation of BM involvement, and this both at diagnosis and during treatment (before ASCC).

Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review. / Dual-Energy-Computertomografie zur Fettquantifizierung in der Leber und im Knochenmark ­ ein Literatur-Review.

BACKGROUND: With dual-energy computed tomography (DECT) it is possible to quantify certain elements and tissues by their specific attenuation, which is dependent on the X-ray spectrum. This systematic review provides an overview of the suitability of DECT for fat quantification in clinical diagnostics compared to established methods, such as histology, magnetic resonance imaging (MRI) and single-energy computed tomography (SECT). METHOD: Following a systematic literature search, studies which validated DECT fat quantification by other modalities were included. The methodological heterogeneity of all included studies was processed. The study results are presented and discussed according to the target organ and specifically for each modality of comparison. RESULTS: Heterogeneity of the study methodology was high. The DECT data was generated by sequential CT scans, fast-kVp-switching DECT, or dual-source DECT. All included studies focused on the suitability of DECT for the diagnosis of hepatic steatosis and for the determination of the bone marrow fat percentage and the influence of bone marrow fat on the measurement of bone mineral density. Fat quantification in the liver and bone marrow by DECT showed valid results compared to histology, MRI chemical shift relaxometry, magnetic resonance spectroscopy, and SECT. For determination of hepatic steatosis in contrast-enhanced CT images, DECT was clearly superior to SECT. The measurement of bone marrow fat percentage via DECT enabled the bone mineral density quantification more reliably. CONCLUSION: DECT is an overall valid method for fat quantification in the liver and bone marrow. In contrast to SECT, it is especially advantageous to diagnose hepatic steatosis in contrast-enhanced CT examinations. In the bone marrow DECT fat quantification allows more valid quantification of bone mineral density than conventional methods. Complementary studies concerning DECT fat quantification by split-filter DECT or dual-layer spectral CT and further studies on other organ systems should be conducted. KEY POINTS: · DECT fat quantification in the liver and bone marrow is reliable.. · DECT is clearly superior to SECT in contrast-enhanced CT images.. · DECT bone marrow fat quantification enables better bone mineral density determination.. · Complementary studies with split-filter DECT or dual-layer spectral CT as well as studies in other organ systems are recommended.. CITATION FORMAT: · Molwitz I, Leiderer M, Özden C et al. Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review. Fortschr Röntgenstr 2020; 192: 1137 - 1152.

Mid-term response assessment in multiple myeloma using a texture analysis approach on dual energy-CT-derived bone marrow images - A proof of principle study.

PURPOSE: To identify textural features on dual-energy CT (DECT)-generated virtual non calcium (VNC) bone marrow images in a small group of patients with multiple myeloma undergoing systemic treatment which could potentially help for mid-term response assessment. METHODS: 44 patients (59.1 ±â€¯11.2 yr.) with multiple myeloma who underwent unenhanced whole-body reduced-dose DECT before and after systemic therapy were evaluated. All patients had current hematologic laboratory tests including serum levels of immunoglobulins, albumin, and total proteins. Using DECT post-processing, bone marrow images of the axial skeleton were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of 1st order (n = 18) and 2nd order Gray Level Co-occurrence Matrix (GLCM) textural features (n = 23) based on an open-source radiomics library (Pyradiomics), which were then compared with the hematologic response category to treatment. Five patients underwent only active surveillance at intervals after previous successful therapy. RESULTS: According to hematologic diagnosis, 29 patients were classified as complete response (CR), 10 as partial response (PR) and 5 as stable disease (SD). We observed a significant drop of the 1st order textural features "10th percentile" (p = 0.009), "median" (p = 0.01), and "minimum" (p < 0.0001) after treatment, whereas the 1st order feature "range" (p = 0.0004) and the 2nd order GLCM feature "difference variance" (p = 0.007) significantly increased in patients experiencing CR. A similar trend, however, without statistical significance, could be observed in patients achieving PR after treatment. 2nd order GLCM feature "difference variance" proved to be a significant discriminator (p = 0.01) between patients with CR and PR (sensitivity 0.93, specificity 0.70) for a cut-off value of -0.28. In patients classified CR, both the mean serum protein and the beta-2 microglobulin decreased after treatment, whereas the serum albumin increased (p < 0.01). The same trend without significance could be observed in patients classified PR. CONCLUSIONS: Changes in textural features applied on VNC bone marrow images in the pre- and posttreatment settings correlate well with myeloma-specific hematologic parameters and provide complementary information for the assessment of the late effects of treatment on the bone marrow.

Visualizing bone tissue in homeostatic and pathological conditions.

The human body is comprised of hundreds of bones, which are constantly regenerated through the interactions of two cell types: osteoblasts and osteoclasts. Given the difficulty of analyzing their intravital dynamics, we have developed a system for intravital imaging of the bone marrow cavity using two-photon microscopy, to visualize the dynamic behaviors of living bone cells without sectioning. Combined with the newly developed chemical fluorescent probes to detect localized acidification caused by osteoclasts, we identified two distinct functional states of mature osteoclasts, i.e., "bone-resorptive" and "non-resorptive". Here, we focus on the dynamics and functions of bone cells within the bone marrow cavity and discuss how this novel approach has been applied to evaluate the mechanisms of action of drugs currently in clinical use. We further introduce our recent study that identified arthritis-associated osteoclastogenic macrophages in inflamed synovium and revealed their differentiation trajectory into the pathological osteoclasts, which together represent to a new paradigm in bone research.

The effects of dietary fatty acids on bone, hematopoietic marrow and marrow adipose tissue in a murine model of senile osteoporosis.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown.Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p<0.001) and bone (bone%;r=-0.344, p=0.013) volume fractions.Adjusting for multiple comparisons, bone% was higher and MAT% was lower in Fish oil (FO)-supplemented groups vs. controls (p<0.001). HBM% did not differ significantly between the four groups. However, in the group supplemented with FO, HBM comprised higher fractions and MAT constituted lower fractions of total marrow vs. controls (p<0.001).Conclusion: Feeding FO-enriched diet prevented age-related bone and HBM loss, by reducing MAT expansion. Our results further emphasize on the role(s) of MAT expansion in bone and HBM atrophy.Methods: SAMP8 mice (n>9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (µCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by primary infiltration of bone marrow and excessive production of abnormal immunoglobulin. This disease is the second most common hematologic malignancy (after lymphoma), and its spectrum of characteristic features are widely known by the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Traditionally, the diagnosis and treatment of MM have been triggered by clear end-organ damage. However, owing to recently introduced treatment options that can extend patient survival and the increasing recognition of biomarkers that can be used to identify patients at high risk of progression to active disease, the diagnostic criteria have been revised. Bone disease is one of the most prominent features of MM, and imaging has an important role in diagnosis and follow-up, with each whole-body imaging modality having different indications in distinct disease situations. Skeletal survey has been the standard imaging procedure used during the past decade, but it should no longer be used unless it is the only option. Whole-body low-dose CT is a reasonable and cost-effective initial imaging approach. Whole-body MRI is the most sensitive technique for detecting bone involvement and assessing painful complications. PET/CT is the best tool for evaluating treatment response. The importance of radiologists has increased in this scenario. Therefore, to properly assist hematologists and improve the care of patients with MM, it is essential that radiologists know the updated diagnostic criteria for MM, indications for and limitations of each imaging option, and recommendations for follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

BACKGROUND: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA. METHODS: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N = 50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling. RESULTS: The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3 years (SD 6.5) and 74% were female. There was no significant difference at 2 years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (- 313.5 mm3, 95% CI -4244.7 to 3617.7). CONCLUSIONS: Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA. TRIAL REGISTRATION: VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/.

MagA increases MRI sensitivity and attenuates peroxidation-based damage to the bone-marrow haematopoietic microenvironment caused by iron overload.

Early evaluation of iron overload (IO) and prompt iron-chelation therapy reduce the haematopoietic damage wrought by IO-induced reactive oxygen species (ROS). We examined whether MagA could simultaneously increase the sensitivity of magnetic resonance imaging (MRI) for iron measurement and attenuate oxidative damage to the haematopoietic microenvironment. After generation of a transgenic (Tg) mouse model, MRI, transmission electron microscopy and cytotoxicity assays were used to assess various parameters in mesenchymal stem cells (MSCs). Transverse relaxation rate (R2*) of MagA-expressing MSCs in the presence of iron supplement was higher compared with that of control cells. Besides, R2* value of liver from IO magA Tg mice was higher than that of wild type mice. Moreover, MagA contributed to reduce the cytotoxicity of iron against MSCs, reduce expression of p-p38 mitogen-activated protein kinase and ferritin, and reduce inhibition of the osteogenic differentiation caused by IO. These data support the use of magA as a reporter gene for cell tracking with MRI and indicate exciting new possibilities for use of MagA in the attenuation of injury due to oxidative stress caused by exogenous iron.

Magnetic Resonance Spectroscopy for Evaluating the Effect of Pulsed Electromagnetic Fields on Marrow Adiposity in Postmenopausal Women With Osteopenia.

OBJECTIVE: Pulsed electromagnetic fields (PEMFs) could promote osteogenic differentiation and suppress adipogenic differentiation in bone mesenchymal stem cells ex vivo. However, data on the effect of PEMF on marrow adiposity in humans remain elusive. We aimed to determine the in vivo effect of PEMF on marrow adiposity in postmenopausal women using magnetic resonance spectroscopy. METHODS: Sixty-one postmenopausal women with osteopenia, aged 53 to 85 years, were randomly assigned to receive either PEMF treatment or placebo. The session was performed 3 times per week for 6 months. All women received adequate dietary calcium and vitamin D. Bone mineral density (BMD) by dual-energy x-ray absorptiometry, vertebral marrow fat content by magnetic resonance spectroscopy, and serum biomarkers were evaluated before and after 6 months of treatment. RESULTS: A total of 27 (87.1%) and 25 (83.3%) women completed the treatment schedule in the PEMF and placebo groups, respectively. After the 6-month treatment, lumbar spine and hip BMD increased by 1.46% to 2.04%, serum bone-specific alkaline phosphatase increased by 3.23%, and C-terminal telopeptides of type 1 collagen decreased by 9.12% in the PEMF group (P < 0.05), whereas the mean percentage changes in BMD and serum biomarkers were not significant in the placebo group. Pulsed electromagnetic field treatment significantly reduced marrow fat fraction by 4.81%. The treatment difference between the 2 groups was -4.43% (95% confidence interval, -3.70% to -5.65%; P = 0.009). CONCLUSIONS: Pulsed electromagnetic field is an effective physiotherapy in postmenopausal women, and this effect may, at least in part, regulate the amount of fat within the bone marrow. Magnetic resonance spectroscopy may serve as a complementary imaging biomarker for monitoring response to therapy in osteoporosis.

Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial.

BACKGROUND: A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers. METHODS/DESIGN: A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (ß = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group. DISCUSSION: To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014.

Multi-spin echo spatial encoding provides three-fold improvement of temperature precision during intermolecular zero quantum thermometry.

PURPOSE: Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR. METHODS: A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples. RESULTS: MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C. CONCLUSION: MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow.

Vertebral Bone Marrow Edema (VBME) in Conservatively Treated Acute Vertebral Compression Fractures (VCFs): Evolution and Clinical Correlations.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To assess (1) the evolution of vertebral bone marrow edema (VBME) in patients with A1 vertebral compression fractures (VCFs) conservatively treated and (2) the relationship between VBME and clinical symptoms, evaluated as Visual Analogue Scale (VAS) back pain and Oswestry Disability Index (ODI). SUMMARY OF BACKGROUND DATA: VBME is a marker of acute-subacute vertebral fractures. Little is known about the evolution of VBME in conservatively managed VCFs, as well as its clinical meaning. METHODS: 82 thoracic or lumbar VCFs (21 post-traumatic; 61 osteoporotic VCFs), type A1 according to the AOSpine thoracolumbar spine injury classification system, in 80 patients were treated with C35 hyperextension brace for 3 months, bed rest for the first 25 days. Patients with osteoporotic fractures also received antiresorptive therapy and vitamin D supplementation. At 0 (T0), 30 (T1), 60 (T2), and 90 (T3) days, patients underwent magnetic resonance imaging evaluation and clinical evaluation, using VAS for pain and ODI.The paired t test was used to compare changes within groups at each follow-up versus baseline. The unpaired t test after ANOVA (analysis of variance) was used to compare the 2 groups at each follow-up.The association between VBME area, VAS score, and ODI score was analyzed by the Pearson correlation test. The tests were 2-tailed with a confidence level of 5%. RESULTS: A significant VBME mean area, VAS, and ODI scores reduction was recorded at 60 and 90-days follow-ups versus baseline. A positive correlation between VBME reduction and clinical symptoms improvement (VAS and ODI scores improvement) was found in both traumatic and osteoporotic VCFs. CONCLUSION: In benign A1 VCFs conservatively managed, VBME slowly decreases in the first 3 months of magnetic resonance imaging follow-up. This VBME reduction is related to clinical symptoms improvement. LEVEL OF EVIDENCE: 4.

The temperature dependence of the speed of sound in bovine bone marrow at 750 kHz.

We present values for the speed of sound (SOS) in bovine bone marrow as a function of temperature between 17 degrees C and 44 degrees C. The measurements were made using a time-of-flight approach on a volume of roughly 10 mL, at 750 kHz. The equipment was validated using both distilled water and castor oil. The results show a linear response with SOS changing from 1456.23 ms(-1) at 17 degrees C to 1342.40 ms(-1) at 44 degrees C. The mean value at 37 degrees C was (1371.91 ms(-1)). The temperature coefficient of the SOS was found to be -4.21 +/- 0.19 ms(-1) degrees C(-1). This was well fitted to a least squares model with R2 = 0.88.

Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation.

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.