Umi Nabilah Ismail1, Che Ahmad Azlan1, Shasha Khairullah2, Kuan Jin Lee3, Chai Hong Yeong4, Nur Farhayu Omar5, Mohammad Nazri M Shah1, Raja Rizal Azman Raja Aman1, Nicholas Jackson6, and Kwan Hoong Ng1
1Biomedical Imaging Department, University of Malaya, Kuala Lumpur, Malaysia, 2Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 3Singapore Bioimaging Consortium, A*STAR Research, Singapore, Singapore, 4School of Medicine, Faculty of Health and Medical Sciences, Taylor's University Lakeside Campus, Subang Jaya, Malaysia, 5Department of Imaging, Universiti Putra Malaysia, Serdang, Malaysia, 6Department of Pathology, University of Malaya, Kuala Lumpur, Malaysia
Synopsis
Fat in bone marrow is stated to be regulated by the body
haematopoietic needs. We explored this by measuring bone marrow fat fraction(FF)
of healthy subjects and β-thalassaemia patients who required treatment to
suppress their body haematopoietic needs. The results obtained from 1H-MR
Spectroscopy suggested that information about marrow adipocytes may be useful
in evaluating patients' treatment response.
Introduction
β-thalassaemia is a genetic disease that
is characterized by an absence or reduction of β-globin chain in haemoglobin which
then resulted in anaemia1. To compensate for the anaemic
condition, the body forces more red blood cells (RBCs) to be produced by the
bone marrow, which cause the erythroid marrow expansion to occur. Blood
transfusion is the main treatment given to patients.
Marrow adipocytes, one of the main
components of bone marrow, are stated to be regulated by the prevailing
requirement for haematopoiesis2. The healthy ageing process has
been associated with an increase in marrow adipocytes and decrease in haematopoietic
needs.
However, in pathologic conditions that can cause an increase in
haematopoietic needs (e.g. anaemia), the fat in bone marrow will decrease. As
blood transfusion given to the patients is aimed to reduce body's
haematopoietic needs, it is expected that the fat in bone marrow can be an
indication for the response of the patients to the treatment given.
Hence, this study aims to investigate
the difference of fat fraction (FF) in proximal femur of healthy subjects and β-thalassaemia
patients.Methodology
1H
MRS Spectra of four healthy subjects and five β-thalassaemia patients who
needed to receive monthly blood transfusion were obtained using STEAM sequence
(TR:3000ms TE: 20,25,30,35 and 40ms and TM: 10ms)3. The spectra were obtained using an 8-channel
phased-array coil with a 3T Siemens MAGNETOM Prisma system. ROIs with 10x10x10
mm were drawn on the femoral head, femoral neck,
diaphysis and greater trochanter for each subject (Fig 1). The spectra were analysed using AMARES algorithm4 included in the jMRUI software package5. A custom-written MATLAB code was used to assume
mono-exponential decay as to obtain T2-corrected fat and water peaks and the mean FFs for each ROI were then computed.Results and Discussion
Fig. 2 shows an example of the
single-voxel STEAM MR Spectra obtained from the diaphysis of healthy subjects
and patients. Fig. 2b is a representative spectrum that occurs due to iron
overload in thalassaemia patients as a result of the blood transfusion they
received while Fig. 2c shows an almost non-existence fat in the diaphysis region
of one of the patients. The difference of FF between healthy group and
β-thalassaemia patients can be observed in Fig. 3 with the FF for patients show
a large variation as compared to healthy subjects.
As fat in bone marrow was expected to be
regulated by body haematopoietic needs, the treatment given to the patients
should allow the FF of patients to be almost similar to healthy subjects.
However, it can be observed that patients (mean FF: 30.5±32.3%) exhibit a low
FF value compared to healthy subjects (mean FF: 92.2±5.7%) and the value of FF
in patients are highly variable (range FF: 0.8 – 85.4%).
Furthermore, the extremely low value of
FFs in some subjects need to be highlighted as the absence
of fat in the bone marrow has been cited to be the cause for extramedullary
haematopoiesis (EMH)6, a known extreme stress response
to hypoxia in β-thalassaemia. Based on this, it is assumed that the treatment
did not completely alleviate the anaemic condition in some patients.
The present analysis still has some
limitations as the relationship between marrow adipocytes and haematopoiesis
has still not been well-established. Moreover, there may be other factors that
influence marrow adipogenesis in β-thalassaemia patients. Other than that,
using MRI multi-point Dixon technique may allow a higher advantage as the
spatial variation of FF in the femur can be obtained.Conclusion
1H MR spectroscopy enables the bone
marrow composition in the proximal femur of healthy and β-thalassaemia groups
to be studied. β-thalassaemia patients show a lower value and wide range of FF
compared to healthy subjects. The wide range of FF may be due to the treatment
given does not equally reduce body haematopoietic needs in all patients. Acknowledgements
We thank Gavin Hamilton (Liver Imaging Group, Department of Radiology, University of California San Diego) for providing technical support and prior knowledge file for spectra analysis. This study was funded by grant RP042C-17AET and BKS050-2017. No other potential conflict of interest relevant to this article was reported.References
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