# Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study

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## Abstract

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## Simple Summary

## Abstract

_{median}measurements of 65 osteoblastic metastases in nine patients, as well as phantom measurements. PSMA-PET served as a surrogate for bone metastasis viability. Measures quantifying repeatability were calculated and differences in mean ADC values according to PSMA-PET status were examined. The relative repeatability coefficient %RC of ADC

_{median}measurements was 5.8% and 12.9% for phantom and in vivo measurements, respectively. ADC

_{median}values of bone metastases ranged from $595\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ to $2090\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ with an average of 63% higher values in nonviable metastases compared with viable metastases (p < 0.001). ADC shows a small repeatability coefficient in relation to the difference in ADC values between viable and nonviable metastases. Therefore, ADC measurements fulfill the technical prerequisite for reliable treatment response evaluation in osteoblastic metastases.

## 1. Introduction

## 2. Materials and Methods

#### 2.1. Study Design, Patients and Imaging Protocol

^{18}F]PSMA-1007 for clinically indicated PSMA-PET. One hour after PET tracer injection, two repeated T1w and DWI MRI measurements were conducted on a Biograph mMR PET-MR-System (Siemens, Erlangen, Germany) to determine in vivo repeatability of DWI measurements. There was no concurrent PET scan at this time. Diffusion acquisition was performed using a Spin-Echo-EPI Sequence (FOV 380 × 275 mm², 21 axial slices, voxel size 2 × 2 × 5 mm³, TE 86 ms, TR 6400 ms, fat suppression SPAIR, 1 × b = 50 s/mm², 3 × 400 s/mm², 3 × 800 s/mm²). ADC-maps were automatically calculated with the standard settings provided by the vendor. For T1, an axial volumetric interpolated breath hold examination (VIBE) sequence was used (FOV: 420 × 342, acquisition matrix: 320 × 224, slice thickness 5 mm, TR 1.96 ms, TR 4.07, no fat suppression). Between the two MRI measurements, the patients were moved out of the MRI, repositioned and moved back in again. The area covered by repeated DWI measurement in each patient can be found in Table 1.

#### 2.2. Phantom Measurements

^{®}Version 7.2.4 (MIM Software Inc., Cleveland, OH, USA).

#### 2.3. Image Analysis

_{mean}and ADC

_{median}) within the VOI were measured. The maximum standardized uptake value ($SU{V}_{max}$) was measured using a VOI on PET images. For lesions showing no tracer accumulation above background, a VOI was drawn in correlation to DWI signal alterations and alterations on T1w images or CT.

#### 2.4. Statistical Analysis

_{median}and ADC

_{mean}is compared with the Wilcoxon signed-rank test. Two-sided p-values are reported for all tests.

## 3. Results

#### 3.1. Phantom Measurements

_{mean}, the mean deviation from the respective target values over all vials was +$23.6\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ and the mean absolute deviation $27.5\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, with a standard deviation of $17.8\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$. The repeatability coefficient averaged over all vials for ADC

_{mean}was $54.3\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ and the %RC was 5.83%.

_{median}, the mean deviation from the respective target values over all vials was +$23.9\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ and the mean absolute deviation $27.8\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, with a standard deviation of $17.8\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$. The repeatability coefficient over all vials for ADC

_{median}was $54\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ and the %RC was 5.81%.

_{mean}and ADC

_{median}, respectively).

#### 3.2. Bone Metastases Characteristics

^{3}[IQR: 1.1–12.8]. The median $SU{V}_{max}$ was 12.1 [IQR: 6.6–17.7].

#### 3.3. Repeatability of ADC Measurements in Bone Metastases

_{mean}and ADC

_{median}was $60\times {10}^{-6}{\mathrm{mm}}^{2}/\mathrm{s}$ and $51\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, respectively (Table 2). Consequently, the repeatability coefficients (RC) for ADC

_{mean}and ADC

_{median}were determined to be $166\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ and $141\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, respectively. Furthermore, the within-subject coefficient of variation (wCV) for ADC

_{mean}and ADC

_{median}was 5.5% and 4.7%, respectively.

_{median}compared with ADC

_{mean}(p = 0.04 for comparison of the SD of repeated measurements of ADC

_{median}and ADC

_{mean}). For this reason, the following analyses were conducted using the ADC

_{median}.

_{median}measurements. In the Bland–Altman analysis, the mean difference between the two repeated measurements was $3.09\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, with limits of agreement of $\pm 141.52\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$. The Bland-Altman analysis showed that the difference between repeated measurements increased with the height of the measured value (correlation between mean and absolute difference ${r}_{Spearman}=0.31,p=0.01$, Figure A1). Expressing the differences as a percentage of their average [35] removed the relationship between repeatability and size of the measurement (${r}_{Spearman}=0.008,p=0.95$, Figure A1). The distance of the limits of agreement to the mean difference of $-0.32\%$ was $\pm 12.60\%$ (95% CI [9.86–15.33], shown in Figure 3), which is very close to the %RC reported in Table 2. Based on these results, wCV and %RC seem suitable to quantify the repeatability of the in vivo measurements.

_{median}measurements was the highest in the thoracic spine, followed by the lumbar spine, and it was the lowest in the pelvic region (Figure 3). However, the differences were not statistically significant ($p=0.18$) with corresponding RCs of $209.0$, $149.7$, and $116.3\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$.

#### 3.4. ADC Range in Bone Metastases and Association with PSMA-PET Uptake

_{median}measurements ranged from $595\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ to $2090\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ (Figure 4). The lowest mean ADC

_{median}was observed in lesions with strong PSMA uptake with $930\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$. A markedly higher mean ADC

_{median}was found in lesions with only faint tracer uptake ($1529\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$) and with PET signal on background level ($1683\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$). According to the linear mixed-model analysis, the ADC

_{median}was on average $64.1\%$ (95% CI [41.6–90.4], $p<0.001$) and $63.2\%$ (95% CI [44.6–84.8], $p<0.001$) higher in lesions with faint tracer uptake and PET signal on background level, respectively.

_{median}can be seen (Figure 3, ${r}_{Spearman}=-0.72$, 95% CI [−0.82–−0.58]).

## 4. Discussion

_{median}compared with ADC

_{mean}($p=0.04$). In contrast, both measures were equally precise in the phantom study. The absence of a difference in the phantom study can be easily explained. Since the vials in the phantom contain a homogenous fluid, every voxel should have the same ADC value under ideal conditions. Image noise and other artifacts should add a random, symmetrically distributed measurement error. Hence, mathematically, ADC

_{mean}and ADC

_{median}should be identical in the phantom study under ideal conditions. In contrast, the situation is fundamentally different in vivo. Focal bone lesions are surrounded by fatty bone marrow in older individuals, who represent the majority of patients with osteoblastic metastases. Due to the fat suppression techniques used in diffusion-weighted MRI, fatty regions have a very low ADC, often zero. Hence, inclusion of surrounding fatty bone marrow into the volume of interest, be it due to imperfect segmentation or partial volume effect, will result in significant outliers in the array of ADC values obtained for the measurement. We believe that the better measurement repeatability observed for ADC

_{median}in vivo is explained by the robustness of the median, as a measure of the average, to outliers, unlike the arithmetic mean.

_{median}, closely aligning with the 4.7% found in our study [40]. Messiou et al. investigated the repeatability of ADC measurements in the pelvic bone marrow of nine healthy volunteers, with a repeated scan performed within a 7-day interval. Their estimated %RC of 14.8% is well in line with our results. Their Bland–Altman limits of agreement of mean ADC of bone marrow in normal subjects, however, are much narrower for absolute measurements ($2.0\pm 86\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$), possibly due to a much smaller range of measured values [28]. Donners et al. assessed the value of multiparametric MRI to identify viable bone metastases for biopsies. In their sample of 43 lesions, they observed lower, though not statistically significant, mean/median ADC in tumor-positive biopsies [41]. In contrast to the studies by Reischauer et al. [40], Messiou et al. [28] and Donners et al. [41], which employed regions of interest (ROI), we used volume of interests (VOIs). Going beyond previous studies, the validity of ADC measurements were ensured in our study by the use of a phantom containing the complete range of measured values found in vivo.

_{median}of $930\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$, and those with uptake on background level one of $1683\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$. In relative terms, the ADC

_{median}of metastases considered nonviable was $63\%$ higher than in those considered viable. Accordingly, a negative correlation between the ADC

_{median}and SUV

_{max}of bone lesions could be shown. Our results corroborate the findings of Perez-Lopez et al., correlating ADC values to the detectability of cancer cells in 43 histologic samples of osteoblastic bone metastases. Median ADC was significantly lower in biopsies with tumor cells versus nondetectable tumor cells ($898\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ vs. $1617\times {10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s},p<0.001)$. Tumor cellularity was inversely correlated with ADC (p < 0.001). In serial biopsies taken in three patients before and after treatment, changes in MRI parameters paralleled histological changes [13]. The same group also showed a correlation between change in median ADC of bone metastases and treatment response in metastasized prostate cancer [21].

_{max}. To our knowledge, this is the first study investigating this relationship. The imperfect correlation indicates that DWI and PSMA-PET could have a complementary value in treatment response assessment in prostate cancer metastases. Further studies should investigate this possibility. Going beyond PSMA-PET, ADC quantification might allow for treatment response assessment in osteoblastic metastases of breast cancer and other cancers which do not express PSMA.

## 5. Conclusions

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

## Abbreviations

ADC | apparent diffusion coefficient |

CI | confidence interval |

CT | computed tomography |

CV | coefficient of variation |

DWI | diffusion-weighted (magnetic resonance) imaging |

ICC | intraclass correlation coefficient |

IQR | interquartile range |

MRI | magnetic resonance imaging |

PET | positron emission tomography |

PSA | prostate-specific antigen |

PSMA | prostate-specific membrane antigen |

PVP | polyvinylpyrrolidone |

RC | repeatability coefficient |

RECIST | Response Evaluation Criteria in Solid Tumors |

SD | standard deviation |

SUV | standardized uptake value |

VOI | volume of interest |

wCV | within-subject coefficient of variation |

wSD | within-subject standard deviation |

## Appendix A

**Table A1.**Deviation of ADC

_{mean}and ADC

_{median}measurements from the target value in the phantom stratified by ADC target values.

ADC_{mean} | ADC_{median} | ||||
---|---|---|---|---|---|

PVP Concentration | Temperature-Adjusted Target Value | Mean Deviation from Target Value | Mean Absolute Deviation from Target Value | Mean Deviation from Target Value | Mean Absolute Deviation from Target Value |

% | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{\mathbf{2}}/\mathrm{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$ |

0 | 2106.00 | 33.81 | 36.28 (24.33) | 33.58 | 36.07 (24.20) |

10 | 1640.00 | 21.69 | 25.20 (17.88) | 21.90 | 25.50 (17.78) |

20 | 1258.00 | 3.50 | 18.54 (10.38) | 3.45 | 18.38 (10.44) |

30 | 886.00 | 16.80 | 19.09 (12.97) | 17.08 | 19.52 (13.09) |

40 | 545.00 | 31.46 | 32.17 (14.45) | 32.38 | 32.68 (14.09) |

50 | 293.00 | 29.13 | 29.13 (9.93) | 30.27 | 30.27 (10.40) |

**Table A2.**Deviation and repeatability of ADC

_{median}measurements in the phantom, stratified by ADC target values.

PVP Concentration | Temperature-Adjusted Target Value | Number of Measurements | SD | RC | CV | %RC |
---|---|---|---|---|---|---|

% | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | % | % | |

0 | 2106.00 | 6 × 5 × 3 | 27.6 (24.1–32.3) | 76.5 (66.7–89.6) | 1.3 (1.1–1.5) | 3.6 (3.1–4.2) |

10 | 1640.00 | 6 × 5 × 2 | 22.1 (18.8–27.0) | 61.4 (52.0–74.8) | 1.3 (1.1–1.6) | 3.7 (3.1–4.5) |

20 | 1258.00 | 6 × 5 × 2 | 21.0 (17.8–25.6) | 58.2 (49.3–71.0) | 1.7 (1.4–2.0) | 4.6 (3.9–5.7) |

30 | 886.00 | 6 × 5 × 2 | 16.2 (13.7–19.7) | 44.9 (38.0–54.7) | 1.8 (1.5–2.2) | 5.0 (4.2–6.1) |

40 | 545.00 | 6 × 5 × 2 | 14.8 (12.5–18.0) | 41.0 (34.7–50.0) | 2.6 (2.2–3.1) | 7.1 (6.0–8.7) |

50 | 293.00 | 6 × 5 × 2 | 10.4 (8.8–12.7) | 28.8 (24.4–35.2) | 3.23 (2.7–4.0) | 9.0 (7.6–11.0) |

**Table A3.**Deviation and repeatability of ADC

_{mean}measurements in the phantom, stratified by ADC target values.

PVP Concentration | Temperature-Adjusted Target Value | Number of Measurements | SD | RC | CV | %RC |
---|---|---|---|---|---|---|

% | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | ${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathbf{mm}}^{2}/\mathbf{s}$ | % | % | |

0 | 2106.00 | 6 × 5 × 3 | 27.7 (24.2–32.5) | 76.8 (66.9–90.0) | 1.3 (1.1–1.5) | 3.6 (3.1–4.2) |

10 | 1640.00 | 6 × 5 × 2 | 22.1 (18.7–26.9) | 61.1 (51.9–74.6) | 1.3 (1.1–1.6) | 3.7 (3.1–4.5) |

20 | 1258.00 | 6 × 5 × 2 | 21.1 (17.9–25.7) | 58.5 (49.6–71.3) | 1.7 (1.4–2.1) | 4.7 (3.9–5.7) |

30 | 886.00 | 6 × 5 × 2 | 15.9 (13.5–19.4) | 44.0 (37.3–53.7) | 1.8 (1.5–2.2) | 4.9 (4.1–6.0) |

40 | 545.00 | 6 × 5 × 2 | 16.0 (13.5–19.5) | 44.3 (37.5–54.0) | 2.8 (2.4–3.4) | 7.7 (6.5–9.4) |

50 | 293.00 | 6 × 5 × 2 | 9.9 (8.4–12.2) | 27.5 (23.3–33.6) | 3.1 (2.6–3.8) | 8.6 (7.3–10.5) |

Thoracic Spine | |||||||||||

(n = 9) | |||||||||||

T1 0 | T2 0 | T3 0 | T4 2 | T5 1 | T6 1 | T7 1 | T8 1 | T9 0 | T10 1 | T11 1 | T12 1 |

Lumbar Spine | |||||||||||

(n = 15) | |||||||||||

L1 3 | L2 2 | L3 6 | L4 2 | L5 2 | |||||||

Pelvis | |||||||||||

(n = 41) | |||||||||||

right iliac bone 13 | left iliac bone 7 | sacral bone 12 | right pubic bone 1 | left pubic bone 2 | right ischium 2 | left ischium 2 | right femur 1 | left femur 1 |

**Figure A1.**(

**A**) Mean of repeated ADC

_{median}measurements versus absolute difference of repeated ADC

_{median}measurements. The dashed line indicates the linear relationship between mean ADC

_{median}and absolute deviation of the repeated measurements. Monotonic association between mean and absolute difference: ${r}_{Spearman}=0.31,p=0.01$. (

**B**) Mean of repeated ADC

_{median}measurements versus absolute difference of repeated ADC

_{median}measurements as a percentage of their mean. The dashed line indicates the linear relationship between mean ADC

_{median}and absolute deviation of the repeated measurements. Monotonic association between mean and absolute difference: ${r}_{Spearman}=0.008,$$p=0.95$.

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**Figure 1.**(

**A**) Repeatability coefficient (RC) with corresponding 95% confidence intervals of ADC measurements as measured with the phantom (p-value of regression slope for target value $p=0.001$ and $p=0.0003$ for $AD{C}_{mean}$ and $AD{C}_{median}$, respectively). (

**B**) %RC with corresponding 95% confidence intervals of ADC measurements as measured with the phantom (p-value of regression slope for target value $p=0.01$ and $p=0.01$ for $AD{C}_{mean}$ and $AD{C}_{median}$, respectively).

**Figure 2.**(

**A**) PSMA-PET CT of the pelvis in a patient with widespread bone metastases of prostate cancer prior to initiation of PSMA therapy showing homogeneous PSMA uptake of the right iliac and sacral bone. (

**B**) The same patient one year later after three cycles of PSMA therapy. Only focal PSMA uptake in the sacral bone and multifocal uptake in the right iliac bone. Large areas of sclerotic bone with perviously high PSMA uptake, now showing at most faint uptake, i.e., considered minimal/nonviable. (

**C**) T1w MRI acquired immediately before PSMA-PET in B, showing widespread sclerosis in the right iliac and scaral bone. Note that it is not possible to differentiate areas with high and low uptake in PSMA-PET. (

**D**) ADC map of the same location. Note the excellent correlation with PSMA-PET. Areas showing vivid uptake in PSMA-PET are depicted in dark gray, corresponding to ADC values around 1000. Areas with no or minimal uptake are depicted in light gray, corresponding to ADC values from 1300 to 1500.

**Figure 3.**(

**A**) Standard deviation (SD) of repeated ADC

_{median}measurements by region. (

**B**) SD of repeated ADC

_{median}measurements dependent on lesion volume. (

**C**) Bland–Altman plot of repeated ADC

_{median}measurements. The mean of the repeated measurements is plotted against the differences as a percentage of their mean. The distance of the limits of agreement to the mean difference of $-0.32\%$ is $\pm 12.60\%$ (95% CI [9.86–15.33]). (

**D**) Correlation of average ADC

_{median}measurement and SUV

_{max}, ${r}_{Spearman}=-0.72$, 95% CI [−0.82–−0.58]).

**Figure 4.**Agreement of ADC

_{median}measurements and association with visually assessed uptake of corresponding metastases in PSMA-PET. The diagonal line indicates perfect agreement of the 1st and 2nd measurement. ICC 0.983 (95% CI [0.972–0.990]). Note the small variation between repeated measurements compared with the range of values and the difference between metastases with strong PSMA uptake and those with low tracer uptake. Compared with lesions with strong PSMA uptake, the ADC

_{median}is on average $64.1\%$ (95% CI [41.6–90.4], $p<0.001$) and $63.2\%$ (95% CI [44.6–84.8], $p<0.001$) higher in lesions with faint tracer uptake and PET signal on background level, respectively, according to a linear mixed-model analysis.

ID | Age | PSA ^{1} | Pretreatments | Area Covered by DWI | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

Years | ng/mL | Px | RTx | LHRH | Abi | Enza | PSMA | RTxB | CTX | Apa | Thorax | Lumbar | Pelvis | |

1 | 77 | 0.34 | x | x | x | x | x | x | x | x | x | x | x | |

2 | 79 | 110.00 | x | x | x | x | x | x | x | x | x | x | ||

3 | 83 | 323.00 | x | x | x | x | x | x | ||||||

4 | 73 | 3.87 | x | x | x | x | x | x | ||||||

5 ^{*} | 53 | 3.98 | x | x | x | x | x | |||||||

6 | 65 | 110.00 | x | x | x | x | x | x | x | |||||

7 | 78 | 407.00 | x | x | x | x | x | x | x | x | ||||

8 | 67 | 3.02 | x | x | x | x | x | |||||||

9 | 74 | 1.49 | x | x | x |

^{1}measured at time of scan. PSA = prostate-specific antigen, Px = prostatectomy, RTx = radiation therapy to prostate region, LHRH = treatment with LHRH agonists, Abi = abiraterone, Enza = enzalutamide, PSMA = 177Lu-PSMA therapy, RTxB = radiation therapy of bone metastases, CTX = taxane-based chemotherapy, Apa = apalutamide, DWI = diffusion-weighted imaging. * Patient five was also treated with Denusomab.

ADC_{mean} | ADC_{median} | |
---|---|---|

wSD (${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$) | 59.95 (51.18–72.37) | 50.71 (43.29–61.22) |

RC (${10}^{-6}\phantom{\rule{0.166667em}{0ex}}{\mathrm{mm}}^{2}/\mathrm{s}$) | 166.18 (141.87–200.61) | 140.56 (120.00–169.68) |

wCV (%) | 5.51 (4.57–6.69) | 4.65 (3.85–5.66) |

%RC (%) | 15.27 (12.66–18.55) | 12.90 (10.68–15.70) |

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## Share and Cite

**MDPI and ACS Style**

Eveslage, M.; Rassek, P.; Riegel, A.; Maksoud, Z.; Bauer, J.; Görlich, D.; Noto, B.
Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study. *Cancers* **2023**, *15*, 3757.
https://doi.org/10.3390/cancers15153757

**AMA Style**

Eveslage M, Rassek P, Riegel A, Maksoud Z, Bauer J, Görlich D, Noto B.
Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study. *Cancers*. 2023; 15(15):3757.
https://doi.org/10.3390/cancers15153757

**Chicago/Turabian Style**

Eveslage, Maria, Philipp Rassek, Arne Riegel, Ziad Maksoud, Jochen Bauer, Dennis Görlich, and Benjamin Noto.
2023. "Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study" *Cancers* 15, no. 15: 3757.
https://doi.org/10.3390/cancers15153757