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Multiparametric Whole-body MRI with Diffusion-weighted Imaging and ADC Mapping for the Identification of Visceral and Osseous Metastases From Solid Tumors

Rationale and Objectives

The purpose of this study was to investigate the use of multiparametric, whole-body, diffusion-weighted imaging (WB-DWI) and apparent diffusion coefficient (ADC) maps with T 2 -weighted magnetic resonance imaging (MRI) at 3T for the detection and monitoring of metastatic disease in patients.

Materials and Methods

Fifty-four participants (32 healthy subjects and 22 patients) were scanned with WB-DWI methods using a 3T MRI scanner. Axial, sagittal, or coronal fat-suppressed T 2 -weighted (T 2 WI), T 1 -weighted (T 1 WI), and DWI images were acquired. Total MRI acquisition and set-up time was approximately 45 minutes. Metastatic disease on MRI was confirmed based on T 2 WI characteristics. The number of lesions was established on computed tomography (CT) or positron emission tomography (PET-CT). Whole-body ADC maps and T 2 WI were constructed, and region-of-interests were drawn in normal and abnormal-appearing tissue for quantitative analysis. Statistical analysis was performed using a paired t tests and P < .05 was considered statistically significant.

Results

There were 91 metastatic lesions detected from the CT or PET-CT with a missed recurrent lesion in the prostate. Multiparametric WB-MRI had excellent sensitivity (96%) for detection of metastatic lesions compared to CT. ADC map values and the ADC ratio in metastatic bone lesions were significantly increased ( P < .05) compared to normal bone. In soft tissue, ADC map values and ratios in metastatic lesions were decreased compared to normal soft tissue.

Conclusion

We have demonstrated that multiparametric WB-MRI is feasible for oncologic staging to identify bony and visceral metastasis in breast, prostate, pancreatic, and colorectal cancers. WB-MRI can be tailored to fit the patient, such that an “individualized patient sequence” can be developed for a comprehensive evaluation for staging and response during treatment.

Introduction

Metastatic disease or local recurrences of cancer have an unfavorable prognosis. Treatment approaches for distant metastases are mostly palliative rather than curative. Skeletal or organ metastasis is usually not detected until clinical symptoms appear, or during initial staging of cancer by imaging . If metastatic disease is found, most patients will receive various systemic therapy regimens, with the goal of ameliorating symptoms and improving survival. Although positron emission tomography-computed tomography (PET-CT) covers most of the body, measures the metabolic activity of a tumor, and is used for staging and treatment response, PET may be limited by other factors, such as high uptake in normal organs, variability in tracer uptake in lesions, increased radiation dose, or indeterminate findings due to the size of the lesion (less than 1 cm) . Therefore, there is a need for an imaging method that achieves global tumor assessment and accurate lesion detection for increased confidence in the detection, characterization, and monitoring of treatment response in metastatic disease without an increase in radiation dose.

To address these challenges, developments in whole-body MRI (WB-MRI) technology have resulted in whole-body coverage using anatomic T 1 - or T 2 -weighted imaging at 1.5T . Some of the improvements are specialized surface coils, continuous table movement (CTM), improved respiratory gating, planning software, and pulse sequences. These system improvements in MRI technology have led to impressive results in both oncological and nononcological applications of WB-MRI compared to more conventional imaging methods . As it turns out, most of the applications have been limited to anatomic and qualitative MRI parameters. There is a growing need to accurately quantify functional properties of the tissue, because these metrics represent early biological changes before anatomic MRI parameters. In particular, advanced quantitative MRI parameters such as diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced-MRI (DCE) can provide metrics of the molecular and vascular characteristics of tumors . There are several reports in the literature about the feasibility of using WB-DWI in different cancers . However, only a few of these WB-DWI methods have been applied to whole-body imaging at 3T . Therefore, we have implemented multiparametric WB-MRI, coupled with DWI and quantitative ADC mapping at 3T, to provide functional and quantitative information about normal and tumor (primary or metastatic) tissue and compare the WB-MRI results to CT or PET-CT results. This development of quantitative DWI WB-MRI provides the opportunity to investigate the detection and characterization of metastatic areas in the body without the need for ionizing radiation.

Materials and Methods

Clinical Subjects

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Metastatic Lesion Classification

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MRI Imaging

WB-MRI Protocol

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Figure 1, Demonstration of multiparametric whole-body magnetic resonance imaging in a normal subject. (a) T2-weighted imaging through the central slices in the body. (b) T1-weighted images and (c) ADC maps of the same location in the normal subject. ADC, apparent diffusion coefficient.

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Proton MR Imaging

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Quantitative Diffusion-Weighted Imaging and Apparent Diffusion Coefficient Mapping

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2D PACE Respiratory Gating

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Computed Tomography and Positron Emission Tomography

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Radiological Image Preprocessing and Analysis

Normal and Lesion Tissue Analysis

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Statistical Analysis

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Results

Clinical Characteristics

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Radiological Metrics

Conventional Metastatic Imaging

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WB-MRI

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Figure 2, Demonstration of whole-body magnetic resonance imaging on a 66-year-old man with metastatic prostate cancer. (a) Axial diffusion imaging through the thorax and pelvis shows multiple metastatic lesions in the ribs, sternum, and vertebrae. (b) Three-dimensional visualization of the thorax showing the metastatic lesions in the chest. (c) T2 and STIR imaging of the spine to correlate the metastatic lesions with the whole-body magnetic resonance imaging. The white arrows demonstrate the metastatic lesions in the ribs, sternum, and vertebrae. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; STIR, short tau inversion recovery. (Color version of figure is available online.)

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Figure 3, Demonstration of the whole-body diffusion-weighted imaging (WB-DWI) in a 46-year-old woman with metastatic breast cancer. (a) Three-dimensional visualization of metastatic lesions using different b-values from the DWI. There are progressive changes in the DWI signal intensity within the metastatic sites (white arrows) of the left pelvis, thoracic and lumbar spine, and liver. (b) A coronal ADC map through the midsection of the patient. (c) Different b-values from WB-DWI sagittal images of the spine showing multiple metastatic regions. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging.

Figure 4, Demonstration of the WB-MRI and PET-CT in a 46-year-old woman with metastatic breast cancer in the liver and pelvis. (a) The white arrows in liver and pelvis show metastatic lesions on PET and T2-weighted images. (b) The PET and ADC maps demonstrate the metastatic lesions (white arrows) in the liver. In the pelvis, the yellow arrows indicate normal bone on the ADC map and PET. The white arrows show the metastatic lesions. (c) The same metastatic sites are noted on the WB-MRI diffusion-weighted images (b = 800) and the ADC map. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; PET-CT, positron emission tomography-computed tomography. (Color version of figure is available online.)

Figure 5, Example of WB-MRI screening in 60-year-old man with a stage T2B, Gleason 9 with increasing prostate-specific antigen, post external beam radiation, and androgen deprivation therapy. (a) CT and whole-body MRI was performed for interrogation of metastatic disease. Potential recurrence was only found in the right peripheral zone on the WB-ADC map and shown in the yellow box. (b) Localized MRI with DWI-ADC and Pharmacokinetic-DCE (PK-DCE) was performed “on the fly” for confirmation of prostate cancer recurrence. (Color version of figure is available online.)

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Diffusion-Weighted Imaging-ADC Mapping

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TABLE 1

Regional ADC Map Values From Healthy Subjects

Normals (n = 32) ADC 10 −3 mm 2 /s ADC 10 −3 mm 2 /s Tissue Normal (Rt) SD (±) Normal (Lt) SD (±) ADC ratio Cerebral cortex 0.83 0.14 0.83 0.06 1.00 Cerebellum 0.68 0.06 0.70 0.06 0.97 Lateral ventricle 3.01 0.41 3.14 0.19 0.96 Breast glandular 1.94 0.33 1.91 0.27 1.02 Gall bladder 2.85 0.28 Liver 1.16 0.22 1.12 0.26 1.04 Spleen 0.79 0.07 Pancreas(tail) 1.40 0.19 Kidney 1.93 0.14 1.94 0.11 0.99 Prostate (PZ) 1.68 0.17 1.69 0.23 0.99 Iliac crest 0.43 0.17 0.45 0.18 0.96 Femur 0.21 0.16 0.23 0.15 0.91 Pelvis 0.43 0.13 0.48 0.18 0.90 Psoas muscle 1.35 0.23 1.34 0.20 1.01 Urinary bladder 3.20 0.21 Uterus 1.27 0.20 Vertebral disk 1.59 0.19 Vertebral bone (cervical) 0.43 0.18 Vertebral bone (thoracic) 0.29 0.20 Vertebral bone (lumbar) 0.33 0.20

ADC, apparent diffusion coefficient; Lt, Left; PZ, peripheral zone; Rt, right; SD, standard deviation.

ADC Ratio = contralateral tissue divided by ipsilateral tissue ADC map values.

TABLE 2

Regional Normal ADC Map Values From Patients

Patients (n = 22) ADC 10 −3 mm 2 /s ADC 10 −3 mm 2 /s Tissue Normal (Rt) SD (±) Normal (Lt) SD (±) ADC ratio Cerebral cortex 0.82 0.08 0.84 0.14 0.98 Cerebellum 0.67 0.12 0.66 0.12 1.02 Lateral ventricle 3.30 0.24 3.23 0.22 1.02 Breast glandular 1.85 0.58 1.61 0.08 1.15 Gall bladder 2.75 0.20 Liver 0.99 0.24 1.01 0.22 0.98 Spleen 0.78 0.11 Pancreas(tail) 1.54 0.24 Kidney 1.85 0.17 1.85 0.13 1.00 Prostate (PZ) 1.45 0.15 1.42 0.10 1.02 Iliac crest 0.31 0.19 0.32 0.20 0.97 Femur 0.17 0.15 0.23 0.17 0.74 Pelvis 0.32 0.14 0.24 0.26 1.33 Psoas muscle 1.19 0.27 1.32 0.19 0.90 Urinary bladder 2.90 0.24 Uterus 1.42 0.13 Vertebral disk 1.53 0.16 Vertebral bone (cervical) 0.60 0.17 Vertebral bone (thoracic) 0.27 0.18 Vertebral bone (lumbar) 0.33 0.21

ADC, apparent diffusion coefficient; Lt, Left; PZ, peripheral zone; Rt, right; SD, standard deviation.

Ratio = contralateral tissue divided by ipsilateral tissue ADC map values.

TABLE 3

ADC Map Values From Metastatic Lesions in Patients

Metastatic Lesions ADC 10 −3 mm 2 /s ADC 10 − mm 2 /s Tissue Lesion SD (±) Normal SD (±) Ratio Vertebral bone (thoracic) 0.82 0.13 0.27 0.18 3.04 Vertebral bone (lumbar) 0.99 0.19 0.33 0.21 3.00 Pelvis 0.90 0.10 0.17 0.15 5.29 Femur 1.60 0.23 0.32 0.14 5.00 Iliac crest 0.84 0.45 0.32 0.07 2.63 Liver 0.88 0.27 1.12 0.26 0.79 Prostate (PZ) 1.00 0.07 1.45 0.15 0.69

ADC, apparent diffusion coefficient; Lt, left; PZ, peripheral zone; Rt, right; SD, standard deviation.

Ratio = Lesion tissue divided by normal tissue ADC.

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ADC Ratios and Standardized Uptake Values in Normal and Lesion Tissue

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Discussion

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Conclusions

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