Figure 1.
Origin of the water-fat iZQC signal from BAT (BATSCI).
(A–B) Histological haematoxylin and eosin (H&E) staining of BAT (A) and white fat (B) from a mouse showing different cell morphologies. Brown fat cells present multiple smaller lipid vacuoles and higher hydration level and are usually smaller than white fat cells, which are made by a single large lipid droplet. (C) Cartoon showing the different cellular structures and the origin of the iZQC signal in BAT: unlike in white fat, in BAT water and fat spins are mixed together at the cellular level such that the selection of a small correlation distance can select the BATSCI signal only from BAT (D) Scheme of the radio frequency pulse sequence used in the experiments for the detection of BAT.
Figure 2.
In vitro detection of excised mouse BAT.
(A) Axial image of three samples containing BAT, WAT, and a mixture of WAT and muscle. (B) Fat fraction as measured by a conventional CSI sequence showing similar water content for the BAT and for the mixed sample. (C) BATSCI image showing the presence of a strong signal only in the BAT sample. (D) BATSCI signal normalized to the nearby fat-fat iZQC signal from different tissues and from different mice. (E) BATSCI signal intensity as function of the correlation distance as obtained from a phantom containing excised mouse BAT.
Figure 3.
In vivo mapping of BAT using the BATSCI method.
(A) BATSCI map in a C57 mouse highlighting the BAT depot. (B) Fat-fat iZQC map on the same C57 mouse highlighting both WAT and BAT depots. (C) Photograph of a Caveolin-1 null mouse showing the interscapular brown fat depot (pale pink). (D) BATSCI map overlapped on the anatomical photograph, highlighting the interscapular BAT depot and the peri-renal BAT depots (not visible in the photograph).
Figure 4.
Correlation between BATSCI maps and the BAT activity maps obtained with 18F-FDG-PET.
(A) Anatomical sagittal spin echo MR image of a young C57 mouse. (B) BATSCI map of the same mouse overlapped to the anatomical image. (C) BATSCI map showing the interscapular brown fat area as well other BAT depots near the neck (D) BAT activity map obtained by 18F-FDG-PET of the same mouse acquired after BAT stimulation. 18F-FDG-PET scans show active BAT as well as other metabolically active (heart and brain) tissues, but not inactive BAT.
Figure 5.
Comparison between BATSCI maps and fat fraction maps for the detection of BAT.
(A) Anatomical sagittal spin echo MR image of a young C57 mouse. (B) Fat fraction map of the same animal. (C) BATSCI map showing the interscapular brown fat depot. (D) BATSCI map overlaid on spin-echo image, illustrating the intrascapular BAT depot. (E) Anatomical coronal spin echo MR image of the same animal. (F) Coronal Fat fraction map of the same animal. (G) BATSCI map showing the interscapular brown fat area. (H) BATSCI map overlaid on spin-echo image, illustrating the intrascapular BAT depot.
Figure 6.
Detection of BAT activity with the BATSCI signal.
(A) Temperature behavior of BAT in a healthy balb/c mouse after stimulation by NE injection showing the effect of the drug. After the injection of the BAT stimulant BAT temperature rises followed by rectal temperature (B) BATSCI signal intensity and T2* -weighted signal intensity from the interscapular BAT as function of time, before during and after stimulation of BAT by NE.
Figure 7.
In vitro detection of human BAT using the BATSCI signal.
(A) Spin echo image of 3 human BAT samples: supraclavicular fat from a 27 year old male (I, bottom left), supraclavicular fat from a 95 year old female (II, bottom right) and abdominal fat from the same 95 year old female (III, top) (B) BATSCI map obtained from the same 3 samples. Only the fat sample excised from the supraclavicular area of the 27 years old male (bottom left) shows a significant BATSCI signal. (C) 2D iZQC spectrum acquired on the 27 year old male supraclavicular fat sample highlighting (yellow box) the region containing the water-fat and the fat-fat iZQC peak. (D) 2D-iZQC spectrum showing the water-fat (BATSCI) and the fat-fat iZQC peak from the supraclavicular fat sample of the 27 year old male, along with the 1H-MRS spectrum (inset). (E) 2D-iZQC spectrum from the supraclavicular fat of the 95 year old female showing a predominant fat-fat iZQC peak, along with the 1H-MRS spectrum (inset). (F) iZQC spectrum from the abdominal area of the 25 year old female showing only a fat-fat iZQC peak, along with the 1H-MRS spectrum (inset). (G–I) Histological haematoxylin and eosin (H&E) staining of BAT from the 27 year old supraclavicular fat (G), the 95 year old supraclavicular fat (H) and 95 year old abdominal fat (I). (L–N) immunohistochemistry of the same samples to detect UCP1 expression.
Figure 8.
Correlation between BATSCI signal intensity and UCP1 expression.
(A) Scatter plot showing the correlation between intensity of UCP1 staining and normalized BATSCI signal intensity (r-square = 0.8, p<0.0001). (B) Scatter plot showing correlation between % of adipocytes tissue stained positive for UCP1 and normalized BATSCI signal intensity (r square = 0.4, p<0.003). (C) Scatter plot showing the correlation between intensity of UCP1 staining and tissue fat fraction (r-square = 0.37, p<0.016). (D) Scatter plot showing correlation between % of adipocytes tissue stained positive for UCP1 and tissue fat fraction (r square = 0.27, p<0.0015).
Figure 9.
In vivo detection of human BAT in a lean subject.
(A) 2D anatomical image showing the selected slice from which iZQC spectra and images were acquired. (B) 2D iZQC spectrum acquired from the neck-supraclavicular area of a young female with a BMI of 19. (C) Scatter plot showing the inverse correlation between subject BMI and normalized BATSCI signal intensity (r-value = 66%, r-square = 43%, p value less than 0.015). Blue solid squares indicate male subjects, while red solid squares indicate female subjects. (D) BATSCI map on the same subject. (E) Overlay of BATSCI on spin-echo axial image with red arrows indicating possible BAT locations. (F) Fat-fat iZQC map on the same subject. (G) Overlay of fat –fat iZQC map on spin-echo axial image.
Figure 10.
In vivo detection of human BAT in a normal weight subject.
(A) 2D anatomical image showing the selected slice from which iZQC spectra and images were acquired. (B) 2D iZQC spectrum acquired from the same slice (neck/supraclavicular area) of a young male with a BMI of 24.5. (C) BATSCI map on the same subject. The BATSCI signal is undetectable and close to the noise level. (D) Fat-fat iZQC map on the same subject. The fat-fat iZQC map highlights mainly the subcutaneous fat layer. (E) Overlay of BATSCI on spin-echo axial image with red arrows indicating possible BAT locations. (F) Overlay of fat –fat iZQC map on spin-echo axial image.