Research ArticleBioengineering

Fluid assessment in dialysis patients by point-of-care magnetic relaxometry

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Science Translational Medicine  24 Jul 2019:
Vol. 11, Issue 502, eaau1749
DOI: 10.1126/scitranslmed.aau1749
  • Fig. 1 MRI pixel-wise analysis of changes within ROIs.

    (A) The five ROIs—whole leg, muscular tissue, subcutaneous tissue, marrow and bone—that were drawn on each slice of each MRI scan. Subcutaneous tissue ROI includes skin, fat, and blood vessels in the fat. Muscular tissue ROI includes muscle, fascia, nerves, and blood vessels. (B) The muscle group ROIs—anterior, lateral, deep posterior, soleus, and gastrocnemius—that were drawn on the first slice of each scan. (C) A histogram of the pixel-wise short (T2,short) and long (T2,long) relaxation values found in the muscular and subcutaneous tissue of a representative participant. The pre-to-post change in (D) T2,short, (E) T2,long, and (F) RAlong for each ROI across all healthy control (HC, n = 7) and hemodialysis (HD, n = 7) participants. Bars represent the mean ± SD. P values were calculated with a two-sample permutation test. For P values calculated with a two-sample Welch test, see table S3. n.s. denotes P ≥ 0.05, *P < 0.05, **P < 0.01.

  • Fig. 2 MRI pixel-wise relaxation times and relative amplitudes.

    (A) Cumulative distribution function (CDF) of the pixel-wise T2,long values found within the entire leg at baseline. The mean and 95% confidence interval (CI) of all participants (n = 14) is in gray. HD1, HD1b, and HD2b relaxation times are shown separately. (B) Table summary of the proBNP and clinical examination results for HD participants (n = 7). The reference range for proBNP is <300 pg/ml. (C) Heatmaps of T2,short and T2,long for a sample healthy control, HD1, and HD2b. Perifascial fluid deposits and/or subcutaneous edema are indicated by arrows. These fluid deposits and edema were not detectable on clinical exam. The average CDF of the pixel-wise RAlong values in the muscle of HC (n = 7) and HD (n = 7) participants at (D) pre- and (E) post-time points. (F) The change in RAlong for HC (n = 5 because HC2 and HC6 are plotted separately and not included in average) and HD (n = 7) participant groups. All CDF figures are plotted as mean ± 95% confidence interval. Quantile regression P values corresponding to cdf plots are summarized in table S4. HC, healthy control; HD, hemodialysis. A “b” in the participant ID indicates a participant’s second study visit for those that completed the study twice.

  • Fig. 3 MRI biexponential ROI results for the muscle.

    (A) The RAlong values of the muscle ROI for each participant (n = 14) before and after dialysis/bed rest. (B) Muscle RAlong values for HC (n = 7) and HD (n = 7) participants at pre- and post-time points. (C) The pre-to-post change in muscle RAlong for HC (n = 7) and HD (n = 7) participants. The central mark in each boxplot indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers that extend to the most extreme values were not considered outliers. P values were calculated using a two-sample permutation test. For P values calculated with a two-sample Welch test, see table S5. *P < 0.05, **P < 0.01. HC, healthy control; HD, hemodialysis.

  • Fig. 4 Portable single-voxel NMR sensor for bedside relaxometry measurements.

    (A) Photo of the complete NMR sensor, RF coil, and side enclosure containing matching circuitry for the coil. A U.S. Quarter is shown for scale. (B) Photo of the NMR sensor with the top and side panels removed. The arrows denote magnetic orientation of each slab. The red ellipsoid above the sensor denotes approximate sensor measurement region. (C) Schematic of the linear Halbach design showing the orientations of the individual magnets as well as the net Bo and B1 fields. (D) Photo of the NMR sensor in use at the hospital for bedside assessment. The participant’s leg is placed on top of the aluminum platform, which slides onto the bed. (E) Sagittal and transverse MRI scans showing the approximate location of the NMR sensor’s measurement voxel in red.

  • Fig. 5 Comparison of T2 relaxation times measured by the NMR sensor and MRI.

    Scatter plot of fit results (n = 6 monoexponential and n = 3 biexponential fit results) for phantoms and ex vivo tissue samples measured on both the NMR sensor and MRI (pixel-by-pixel method). Correlation between the MRI and NMR sensor values is r2 = 0.966. Vertical (NMR sensor) error bars represent the 95% confidence interval for the fit. Horizontal (MRI) error bars represent the SD of the pixel-by-pixel MRI results.

  • Fig. 6 NMR sensor results and future sensor design criteria.

    (A) Boxplots displaying the pre-to-post change in NMR sensor’s RAb values for HC (n = 7) and HD (n = 7) participants. (B) Change in RAb values plotted the change in ECF-associated resistance, Re, leg (r2 = 0.477) (n = 13 because BI sensor malfunctioned during HC6 post measurement). (C) Boxplots displaying the NMR sensor’s RAb values at pre- and post-time points for HC (n = 7) and HD (n = 7) participants. The central mark in each box plot indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers that extend to the most extreme values were not considered outliers. P values for (A) and (C) were calculated using a two-sample permutation test. For P values calculated with a two-sample Welch test, see table S8. (D) NMR sensor’s RAc plotted against subcutaneous tissue thickness (r2 = 0.672, n = 14). The tissue thickness gets compressed by a few millimeters when the leg is pressed against the NMR sensor’s hard surface during measurement. (E) MRI scan (transverse cross section of the calf) showing the size and location of the four smaller MRI ROIs that were analyzed. (F) Summary of P values showing the ability of the smaller ROIs [in (C)] to distinguish between euvolemic HC (n = 7) and hypervolemic HD (n = 7) participants. P values were calculated using a two-sample permutation test. For P values calculated with a two-sample Welch test, see tables S9 to S12. *P < 0.05. HC, healthy control; HD, hemodialysis.

  • Fig. 7 Whole-body and leg BI results.

    (A to H) Top two quadrants: Raw BI resistance measurements (Re and Rinf). (I to P) Bottom two quadrants: Volume measurements (ECF and TBW) (n = 7 HC, n = 7 HD). (A) to (D) and (I) to (L) (the two left quadrants) come from whole-body BI measurements, whereas (E) to (H) and (M) to (P) (the two right quadrants) come from leg segmental BI measurements. The top row of panels within each quadrant shows Re /ECF data. The bottom row of panels within each quadrant shows Rinf /TBW data. Low in vivo resistance measurements indicate that more fluid is present in the body. Higher resistance measurements indicate that less fluid is present. An increase in resistance indicates a decrease of fluid. Statistics were calculated with both a two-sample Welch test and two-sample permutation test for all plots. The significance level was the same for both statistical tests across all plots except for subplot (N), where the permutation test was significant (P = 0.014) but Welch test was not (P = 0.054). P values for (A) to (H) are summarized in tables S13 to S16. The P value for (J) is P = 0.027. n.s. indicates P > 0.05, *P < 0.05, **P < 0.01. HC, healthy control; HD, hemodialysis.

  • Table 1 Demographics of study population.

    Hypervolemic patients with ESRD treated with hemodialysis (HD) and euvolemic healthy controls (HC) were recruited for the study. One HC participant and two HD participants completed the study twice. Reported blood value results are from baseline blood draws. Fluid loss (in kilograms) is based on the change between pre- and post-weight measurement. Percentage fluid loss is calculated by 100% * fluid loss/(0.6 * baseline weight), because about 60% of the body is water. Values represent mean ± SD. NA, not applicable.

    Reference rangeHealthy control
    (HC) participants
    Hemodialysis
    (HD) participants
    n#7 (6 unique)7 (5 unique)
    Ageyears54.2 ± 4.955.1 ± 10.3
    % White85.7%42.9%
    BMIkg/m218.5–24.925.1 ± 4.427.8 ± 5.0
    Baseline weightkg75.4 ± 12.282.8 ± 16.1
    Fluid losskg0.6 ± 0.22.2 ± 1.2
    Fluid loss%1.2 ± 0.54.3 ± 2.5
    HD vintageDaysNA1013 ± 699.8
    SodiummM134–144140.6 ± 2.1139.1 ± 1.6
    BUNmg/dl6–2416.0 ± 4.458.1 ± 14.5
    Creatininemg/dl0.76–1.270.8 ± 0.28.3 ± 1.8
    WBC×103/ul3.4–10.85.0 ± 1.67.6 ± 1.1
    Platelets×103/ul150–379255.3 ± 77.1184.3 ± 87.4
    OsmolalitymOsm/kg275–295291.6 ± 5.8307.7 ± 4.1
    proBNPpg/ml<30018.4 ± 5.46086.1 ± 4495.9

Supplementary Materials

  • stm.sciencemag.org/cgi/content/full/11/502/eaau1749/DC1

    Computer code for statistical tests

    Fig. S1. Pixel-wise heatmap of MRI biexponential T2 fit results.

    Fig. S2. Histogram of MRI pixel-wise T2 relaxation time values in muscular and subcutaneous tissue at baseline.

    Fig. S3. Histogram of MRI pixel-wise T2 relaxation time values in muscular tissue.

    Fig. S4. Histogram of MRI pixel-wise T2 relaxation time values in subcutaneous tissue.

    Fig. S5. Histogram of MRI pixel-wise RAlong values in muscular tissue.

    Fig. S6. Histogram of MRI pixel-wise RAlong values in subcutaneous tissue.

    Fig. S7. CDFs of MRI pixel-wise RAlong values in muscular tissue.

    Fig. S8. T2 decays of phantoms measured on MRI and NMR sensor.

    Fig. S9. T2 results of phantoms measured on MRI and NMR sensor.

    Fig. S10. Quantitative NMR relaxometry findings at different fluid states.

    Fig. S11. Pixels deleted by the MRI pixel-wise fitting criteria.

    Fig. S12. Bo magnetic field map of the NMR sensor.

    Fig. S13. NMR sensor T2 decay signal from a representative HC and HD participant.

    Table S1. Individual-level demographics of the study population.

    Table S2. F test comparison of multiexponential fits for pixel-wise MRI data.

    Table S3. Summary of change in pixel-wise MRI values within ROIs.

    Table S4. Summary of quantile regression results for MRI pixel-wise RAlong values from the muscle ROI.

    Table S5. Summary of MRI RAlong values for muscle (whole ROI average).

    Table S6. Comparison of specifications of the NMR sensor with those of a traditional MRI scanner.

    Table S7. Summary of phantom T2 relaxation time results for MRI and NMR sensor.

    Table S8. Summary of RAb values from NMR sensor.

    Table S9. Summary of RAlong values from MRI small voxel: Anterior 1 with subcutaneous and muscle.

    Table S10. Summary of RAlong values from MRI small voxel: Anterior 2 with muscle only.

    Table S11. Summary of RAlong values from MRI small voxel: Lateral 1 with subcutaneous and muscle.

    Table S12. Summary of RAlong values from MRI small voxel: Lateral 2 with muscle only.

    Table S13. Summary of whole-body Re BI values.

    Table S14. Summary of whole-body Rinf BI results.

    Table S15. Summary of leg segmental Re BI results.

    Table S16. Summary of leg segmental Rinf BI results.

    Table S17. Change in T2 relaxation time of phantom measured with each human NMR sensor measurement.

  • The PDF file includes:

    • Computer code for statistical tests
    • Fig. S1. Pixel-wise heatmap of MRI biexponential T2 fit results.
    • Fig. S2. Histogram of MRI pixel-wise T2 relaxation time values in muscular and subcutaneous tissue at baseline.
    • Fig. S3. Histogram of MRI pixel-wise T2 relaxation time values in muscular tissue.
    • Fig. S4. Histogram of MRI pixel-wise T2 relaxation time values in subcutaneous tissue.
    • Fig. S5. Histogram of MRI pixel-wise RAlong values in muscular tissue.
    • Fig. S6. Histogram of MRI pixel-wise RAlong values in subcutaneous tissue.
    • Fig. S7. CDFs of MRI pixel-wise RAlong values in muscular tissue.
    • Fig. S8. T2 decays of phantoms measured on MRI and NMR sensor.
    • Fig. S9. T2 results of phantoms measured on MRI and NMR sensor.
    • Fig. S10. Quantitative NMR relaxometry findings at different fluid states.
    • Fig. S11. Pixels deleted by the MRI pixel-wise fitting criteria.
    • Fig. S12. Bo magnetic field map of the NMR sensor.
    • Fig. S13. NMR sensor T2 decay signal from a representative HC and HD participant.
    • Legend for table S1
    • Table S2. F test comparison of multiexponential fits for pixel-wise MRI data.
    • Table S3. Summary of change in pixel-wise MRI values within ROIs.
    • Table S4. Summary of quantile regression results for MRI pixel-wise RAlong values from the muscle ROI.
    • Table S5. Summary of MRI RAlong values for muscle (whole ROI average).
    • Table S6. Comparison of specifications of the NMR sensor with those of a traditional MRI scanner.
    • Table S7. Summary of phantom T2 relaxation time results for MRI and NMR sensor.
    • Table S8. Summary of RAb values from NMR sensor.
    • Table S9. Summary of RAlong values from MRI small voxel: Anterior 1 with subcutaneous and muscle.
    • Table S10. Summary of RAlong values from MRI small voxel: Anterior 2 with muscle only.
    • Table S11. Summary of RAlong values from MRI small voxel: Lateral 1 with subcutaneous and muscle.
    • Table S12. Summary of RAlong values from MRI small voxel: Lateral 2 with muscle only.
    • Table S13. Summary of whole-body Re BI values.
    • Table S14. Summary of whole-body Rinf BI results.
    • Table S15. Summary of leg segmental Re BI results.
    • Table S16. Summary of leg segmental Rinf BI results.
    • Table S17. Change in T2 relaxation time of phantom measured with each human NMR sensor measurement.

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Table S1 (Microsoft Excel format). Individual-level demographics of the study population.

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