Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis

Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberto; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

doi:10.1182/blood-2015-01-618215

Cited by 23 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This computational approach is commonly used in commercially available software for 3D representation of the skeleton, and its potential has been previously validated in our laboratory for the characterization of intraosseous volume and bone marrow metabolic activity [15, 25, 26]. However, thresholding the Hounsfield values on the CT images is not effective in this application since the spinal canal is not directly surrounded by osseous tissue in all slices.…”

Section: Discussionmentioning

confidence: 99%

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis

Marini

Cistaro²,

Campi

et al. 2016

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

PurposeIn amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms.MethodsA new computational three-dimensional method to extract the spinal cord from 18F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, 18F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver.ResultsUptake of 18F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. 18F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis.ConclusionOur computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

show abstract

Section: Discussionmentioning

confidence: 99%

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis

Marini

Cistaro²,

Campi

et al. 2016

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

show abstract

“…Using a dedicated software, capable of quantifying volumes of compact (CBV) and trabecular bone (IBV) from X-ray CT slices 22 – 24 , we already documented a selective erosion of compact bone, which managed to predict patients’ disease-specific survival, providing prognostic information independent from the commonly employed biomarkers 23 . Similarly, Lagenberg et al .…”

Section: Introductionmentioning

confidence: 99%

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway

Marini

Bruno

Fiz

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.

show abstract

“…This could give a platform for second generation clinical trials with dose escalation on either RM or YM, dependent on previously achieved clinical data. Recent FDG-PET/CT indicates potential re-distribution of bone marrow after bone marrow transplant (29). The DECT with lower cost and reduced dose exposure, may be easily incorporated in patient management to measure Post-TMI/bone marrow transplant redistribution of marrow compositions and bone damage, similar to our recent report (16).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Magome

Takahashi

Arentsen

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

Purpose To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition. Methods and Materials Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components (namely; bone, red marrow (RM), and yellow marrow (YM)). DECT derived marrow fat fraction was validated using histology of lumbar vertebrae harvested from cadaver. Fraction of RM (RMF=RM/total marrow) and YMF were calculated in each skeletal region to assess correlation of marrow composition with sites and age. Treatment planning was simulated to target irradiation differentially at higher dose (18 Gy) to either RM or YM and lower dose (12 Gy) to rest of the skeleton. Results A significant correlation between fat fractions obtained from DECT and cadaver histology samples was observed (r=0.861, p< 0.0001, Pearson). The RMF decreased in the head, neck and chest was significantly inversely correlated with age, but did not show any significant age-related changes in abdomen and pelvis regions. Conformity of radiation to targets (RM, YM) was significantly dependent on skeletal sites. The radiation exposure was significantly reduced (p< 0.05, t-test) to organs at risk (OARs) in RM and YM irradiation compared with standard total marrow irradiation (TMI). Conclusions Whole-body DECT offers a new imaging technique to visualize and measure skeletal-wide marrow composition. The DECT based treatment planning offers volumetric and site-specific precise radiation dosimetry of red and yellow marrow which varies with aging. Our proposed method could be used as a functional compartment of TMI for further targeted radiation to specific bone marrow environment, dose escalation, and/or reduction of doses to OARs.

show abstract

Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis

Abstract: Key Points Allogeneic hematopoietic stem cells colonize, other than axial niches, appendicular BM that is abandoned in normal subjects. Bone marrow expansion into distal sites differs between cord blood and adult hematopoietic stem cells.

Cited by 23 publications

References 28 publications

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Contact Info

Product

Resources

About