Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids

Abstract

Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, P < .01) and QAT (mean, 78 msec ± 2, five regions, P < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT (P = .01 and P = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue. Online supplemental material is available for this article.

Conflict of interest statement

Disclosures of Conflicts of Interest: R.O. disclosed no relevant relationships. A.H. disclosed no relevant relationships. J.M. disclosed no relevant relationships. K.Z.A. disclosed no relevant relationships. J.F.E. disclosed no relevant relationships. Z.A.S. disclosed no relevant relationships. K.Y.C. Activities related to the present article: institution receives intramural research program funding from National Institutes of Health. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. A.M.C. disclosed no relevant relationships. A.M.G. disclosed no relevant relationships.

Figures

Graphical abstract

Figure 1:

A–C, Proton density fat fraction (PDFF) images used for MR spectroscopy planning and, D, PET/CT image for retrospective brown adipose tissue activity confirmation. High-spatial-resolution water-fat MRI-derived coronal (A), oblique transverse (B), and oblique coronal (C) PDFF maps (resolution, 1.4 × 1.4 × 3.0 mm) in 24-year-old man with location of proton MR spectroscopy volume cross-section with images shown as black boxes (at gray arrow). Oblique transverse map (B) was prescribed from coronal image (A). Object on top is saline bag used for coil loading and stabilization. Oblique coronal map (C) was prescribed from image B. D, Fluorine 18 fluorodeoxyglucose (FDG) PET/CT image recorded in separate session after cold stimulation (not available to MR spectroscopy operator at time of examination). SUV = standard uptake value. E, Graph shows CT attenuation as function of FDG PET standard uptake value (SUV) within regions of interest retrospectively matched to proton MR spectroscopy volume locations. Symbols and error bars represent means and ranges for CT attenuation in Hounsfield units (vertical axis) and FDG uptake (horizontal axis, logarithmic scale) for region of interest matched to proton MR spectroscopy volumes. Blue symbols are for regions classified as quiescent adipose tissue (n = 5), and black symbols represent regions classified as brown adipose tissue (n = 24). Dashed line is drawn at a glucose uptake of 1.5 SUV, the Brown Adipose Reporting Criteria in Imaging Studies 1.0 criterion for counting FDG PET image pixels as brown adipose tissue in lean participants.

Figure 2a:

Analysis of proton MR spectra of brown adipose tissue. (a) Triglyceride molecule with one of the fatty acids shown in detail with peak labels A–H for individual lipid components. A is methyl proton −CH3. B1 and B2 are methylene proton −(CH2)n. C is methylene protons β to COO. D is methylene protons α to HC=CH. E is methylene protons α to COO. F is diallylic methylene protons. G1, G2, and G3 are glycerol. H is vinylic protons HC=CH. (b) Chemical shift spectra, in parts per million (ppm), of individual fitted components of fit model used in advanced method for accurate, robust, and efficient spectral fitting of MR spectroscopy data color coded and labeled as in a. Overlapping peaks for glycerol protons G1, G2, and G3 and for water are offset for clarity. H2O peak was fitted with combination of Lorentzian and Gaussian line shape H2OL and H2OG, and resulting peak areas were summed for estimates of relaxation parameters and water content. (c) Detail of fitting of two Gaussian peaks (B1 and B2) to asymmetric methylene signal. Matlab reconstruction of the (CH2)n signal from two fitted components was used to find line width (fwhh) and true fitted peak maximum position (fhmax). Exact frequencies at half height were determined by linear interpolation between closest in points in 4096 point and 1500 Hz digitization of model spectrum. (d) Results of time domain data fitting for representative brown adipose tissue spectrum (repetition time sec/echo time msec, 0.8/24; signal-to-noise ratio, 444; methylene line width, 31 Hz) recorded at echo time of 24 msec with measured data (black line), fitted model spectrum (red line), and fit residual (green line) (all shown at same scale) and were recorded at 1500 Hz spectral width of 1024 points and reconstructed with 4096 points and 2 Hz line broadening.

Figure 2b:

Analysis of proton MR spectra of brown adipose tissue. (a) Triglyceride molecule with one of the fatty acids shown in detail with peak labels A–H for individual lipid components. A is methyl proton −CH3. B1 and B2 are methylene proton −(CH2)n. C is methylene protons β to COO. D is methylene protons α to HC=CH. E is methylene protons α to COO. F is diallylic methylene protons. G1, G2, and G3 are glycerol. H is vinylic protons HC=CH. (b) Chemical shift spectra, in parts per million (ppm), of individual fitted components of fit model used in advanced method for accurate, robust, and efficient spectral fitting of MR spectroscopy data color coded and labeled as in a. Overlapping peaks for glycerol protons G1, G2, and G3 and for water are offset for clarity. H2O peak was fitted with combination of Lorentzian and Gaussian line shape H2OL and H2OG, and resulting peak areas were summed for estimates of relaxation parameters and water content. (c) Detail of fitting of two Gaussian peaks (B1 and B2) to asymmetric methylene signal. Matlab reconstruction of the (CH2)n signal from two fitted components was used to find line width (fwhh) and true fitted peak maximum position (fhmax). Exact frequencies at half height were determined by linear interpolation between closest in points in 4096 point and 1500 Hz digitization of model spectrum. (d) Results of time domain data fitting for representative brown adipose tissue spectrum (repetition time sec/echo time msec, 0.8/24; signal-to-noise ratio, 444; methylene line width, 31 Hz) recorded at echo time of 24 msec with measured data (black line), fitted model spectrum (red line), and fit residual (green line) (all shown at same scale) and were recorded at 1500 Hz spectral width of 1024 points and reconstructed with 4096 points and 2 Hz line broadening.

Figure 2c:

Analysis of proton MR spectra of brown adipose tissue. (a) Triglyceride molecule with one of the fatty acids shown in detail with peak labels A–H for individual lipid components. A is methyl proton −CH3. B1 and B2 are methylene proton −(CH2)n. C is methylene protons β to COO. D is methylene protons α to HC=CH. E is methylene protons α to COO. F is diallylic methylene protons. G1, G2, and G3 are glycerol. H is vinylic protons HC=CH. (b) Chemical shift spectra, in parts per million (ppm), of individual fitted components of fit model used in advanced method for accurate, robust, and efficient spectral fitting of MR spectroscopy data color coded and labeled as in a. Overlapping peaks for glycerol protons G1, G2, and G3 and for water are offset for clarity. H2O peak was fitted with combination of Lorentzian and Gaussian line shape H2OL and H2OG, and resulting peak areas were summed for estimates of relaxation parameters and water content. (c) Detail of fitting of two Gaussian peaks (B1 and B2) to asymmetric methylene signal. Matlab reconstruction of the (CH2)n signal from two fitted components was used to find line width (fwhh) and true fitted peak maximum position (fhmax). Exact frequencies at half height were determined by linear interpolation between closest in points in 4096 point and 1500 Hz digitization of model spectrum. (d) Results of time domain data fitting for representative brown adipose tissue spectrum (repetition time sec/echo time msec, 0.8/24; signal-to-noise ratio, 444; methylene line width, 31 Hz) recorded at echo time of 24 msec with measured data (black line), fitted model spectrum (red line), and fit residual (green line) (all shown at same scale) and were recorded at 1500 Hz spectral width of 1024 points and reconstructed with 4096 points and 2 Hz line broadening.

Figure 2d:

Analysis of proton MR spectra of brown adipose tissue. (a) Triglyceride molecule with one of the fatty acids shown in detail with peak labels A–H for individual lipid components. A is methyl proton −CH3. B1 and B2 are methylene proton −(CH2)n. C is methylene protons β to COO. D is methylene protons α to HC=CH. E is methylene protons α to COO. F is diallylic methylene protons. G1, G2, and G3 are glycerol. H is vinylic protons HC=CH. (b) Chemical shift spectra, in parts per million (ppm), of individual fitted components of fit model used in advanced method for accurate, robust, and efficient spectral fitting of MR spectroscopy data color coded and labeled as in a. Overlapping peaks for glycerol protons G1, G2, and G3 and for water are offset for clarity. H2O peak was fitted with combination of Lorentzian and Gaussian line shape H2OL and H2OG, and resulting peak areas were summed for estimates of relaxation parameters and water content. (c) Detail of fitting of two Gaussian peaks (B1 and B2) to asymmetric methylene signal. Matlab reconstruction of the (CH2)n signal from two fitted components was used to find line width (fwhh) and true fitted peak maximum position (fhmax). Exact frequencies at half height were determined by linear interpolation between closest in points in 4096 point and 1500 Hz digitization of model spectrum. (d) Results of time domain data fitting for representative brown adipose tissue spectrum (repetition time sec/echo time msec, 0.8/24; signal-to-noise ratio, 444; methylene line width, 31 Hz) recorded at echo time of 24 msec with measured data (black line), fitted model spectrum (red line), and fit residual (green line) (all shown at same scale) and were recorded at 1500 Hz spectral width of 1024 points and reconstructed with 4096 points and 2 Hz line broadening.

Figure 3:

Flowchart of study. Adipose tissue was targeted for localized MR spectroscopy (MRS) using water-fat MRI in left and right clavicular areas or distal subcutaneous white adipose tissue. After MRI examination, participants were exposed to cold and scanned with fluorine 18 fluorodeoxyglucose PET/CT for glucose uptake to identify brown adipose tissue (BAT) as reference standard. FN = false-negative, FP = false-positive, NP = number of participants, TN = true-negative, TP = true-positive.

Figure 4a:

Localized proton MR spectroscopy relaxation measurement series of brown adipose tissue (BAT) and white adipose tissue (WAT). TE = echo time, TR = repetition time. (a) Echo time series spectra in arbitrary signal intensity units against chemical shift in parts per million (ppm) from BAT in volume shown in Figure 1. This representative BAT series had methylene peak line width of 31 Hz, in the shortest echo time spectrum. This was close to median value of 32 Hz (range, 20–63 Hz) for all BAT volumes. Methylene signal-to-noise ratio in time domain of 479 versus median for all BAT of 414 (range, 238–887). (b) Echo time series spectra recorded from distal subcutaneous WAT. For each series, short repetition time spectra and fully relaxed single-shot spectrum are scaled to the same noise level. Noise level after averaging four signals is half that of single shot fully relaxed acquisition. All spectra were recorded at 1024 point resolution and Fourier transformed at 4096 point resolution with 2-Hz line broadening.

Figure 4b:

Localized proton MR spectroscopy relaxation measurement series of brown adipose tissue (BAT) and white adipose tissue (WAT). TE = echo time, TR = repetition time. (a) Echo time series spectra in arbitrary signal intensity units against chemical shift in parts per million (ppm) from BAT in volume shown in Figure 1. This representative BAT series had methylene peak line width of 31 Hz, in the shortest echo time spectrum. This was close to median value of 32 Hz (range, 20–63 Hz) for all BAT volumes. Methylene signal-to-noise ratio in time domain of 479 versus median for all BAT of 414 (range, 238–887). (b) Echo time series spectra recorded from distal subcutaneous WAT. For each series, short repetition time spectra and fully relaxed single-shot spectrum are scaled to the same noise level. Noise level after averaging four signals is half that of single shot fully relaxed acquisition. All spectra were recorded at 1024 point resolution and Fourier transformed at 4096 point resolution with 2-Hz line broadening.

Figure 5a:

Matched comparisons of 20 fluorine 18 fluorodeoxyglucose PET/CT active brown adipose tissue (BAT) regions in 13 individuals with white adipose tissue (WAT) regions in same individuals. (a) Graph shows T2 of (CH2)n fatty acid chain. (b) Graph shows ratio of relaxation-corrected proton densities of diallylic methylene peak F (unique for polyunsaturated fatty acid [PUFA]) with peak E of methylene α to fatty acid carboxyl group (of which there is one per fatty acid chain). F/E = ratio of peak F to peak E.

Figure 5b:

Matched comparisons of 20 fluorine 18 fluorodeoxyglucose PET/CT active brown adipose tissue (BAT) regions in 13 individuals with white adipose tissue (WAT) regions in same individuals. (a) Graph shows T2 of (CH2)n fatty acid chain. (b) Graph shows ratio of relaxation-corrected proton densities of diallylic methylene peak F (unique for polyunsaturated fatty acid [PUFA]) with peak E of methylene α to fatty acid carboxyl group (of which there is one per fatty acid chain). F/E = ratio of peak F to peak E.

Figure 6a:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).

Figure 6b:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).

Figure 6c:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).

Figure 6d:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).

Figure 6e:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).

Figure 6f:

Separation of brown adipose tissue (BAT), quiescent adipose tissue (QAT), and white adipose tissue (WAT) on basis of fat content (proton density fat fraction [PDFFs]) or T2 of fatty acid methylene peak. (a) Two-dimensional scatter plot shows MR spectroscopy–derived PDFFS as function of T2 of (CH2)n fatty acid chain protons for fluorine 18 fluorodeoxyglucose PET/CT active BAT, supraclavicular adipose regions in participants showing no cold-induced activity in PET (QAT), and distal subcutaneous white adipose tissue (WAT). Plot shows all observations for BAT (n = 67, red circles), QAT (n = 15, blue squares), and WAT (n = 46, black triangles). Means and standard deviations for these three groups are shown as larger open symbols and error bars in their corresponding colors and shape. (b) Box-and-whisker plot of all observations of T2 of fatty acid methylene peak for BAT, QAT, and WAT. Upper and lower bounds in box are quartiles, and notch indicates median. Whiskers show data limits without outliers. Data points have same markers and colors as in a, and markers for data points beyond 1.5 times the interquartile range are filled. P values were calculated with three-way comparison analysis of variance. (c, d) Receiver operating characteristic curves for identification of adipose tissue as BAT or as not cold-activatable adipose tissue (QAT or WAT) using T2 of fatty acid methylene resonance (T2 CH2) (c) and fat content (MR spectroscopy–derived PDFFS) (d). The same 67 data points for BAT and the 61 data points for QAT and WAT shown in a were used to generate receiver operating characteristic curves for T2 of (CH2)n fatty acid protons (area under the curve, 0.95; 95% CI: 0.90, 0.98) and for MR spectroscopy–derived proton density fat fraction (area under the curve, 0.83; 95% CI: 0.75, 0.89). Youden optimum cut-off point for T2 is 76 msec for sensitivity of 85% (95% CI: 74, 93) and specificity of 95% (95% CI: 86, 99) and is indicated by red dot. Receiver operating characteristic curve for MR spectroscopy–derived PDFF has an optimum cut-off at PDFF equal to 89% for sensitivity of 100% (95% CI: 95, 100) and specificity of 52% (95% CI: 38, 65). (e, f) Receiver operating characteristic curves for T2 of fatty acid methylene resonance (T2 CH2) (e) and MR spectroscopy–derived PDFFS (f) with reduced number of data points by averaging repeat measurements per MR spectroscopy location. Receiver operating characteristic for methylene T2 (e) had area under the curve of 0.98 (95% CI: 0.98, 1.00); cut-off was 76 msec for sensitivity of 88% (95% CI: 68, 100) and specificity of 100% (95% CI: 85, 100). Receiver operating characteristic for MR spectroscopy–derived PDFF (f) had area under the curve of 0.86 (95% CI: 0.73, 0.95); cut-off was 84% for sensitivity of 79% (95% CI: 58, 93) and specificity of 77% (95% CI: 55, 92). Again, area under the curve for methylene T2 was better than for MR spectroscopy–derived proton density fat fraction (P < .001).