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Non-gaussian IVIM imaging biomarkers can non-invasively predict the aggressiveness of small papillary thyroid cancers
David Aramburu Nuñez1, Yonggang Lu2, Vaios Hatzoglou3, Andre L Moreira4, Hilda E Stambuk3, Ramesh Paudyal1, Yousef Mazaheri3, Mithat Gonen5, Joseph O Deasy1, Ronald A Ghossein6, Ashok R Shaha7, Michael Tuttle8, and Amita Shukla-Dave1,3

1Medical Physics, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States, 2Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States, 3Radiology, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States, 4Pathology, NYU Langone Medical Center, NEW YORK, NY, United States, 5Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States, 6Pathology, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States, 7Surgery, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States, 8Medicine, Memorial Sloan-Kettering Cancer Center, NEW YORK, NY, United States

Synopsis

There is a need for non-invasive imaging to identify patients with aggressive tumors in papillary thyroid carcinoma (PTC). This study evaluates whether non-gaussian intravoxel incoherent motion (NG-IVIM) DW-MRI has the potential to stratify tumor aggressiveness in PTC. Twenty-four PTC patients underwent pretreatment NG-IVIM DW-MRI at 3T. The apparent diffusion coefficient (ADC), perfusion factor (f), diffusion (D), pseudo diffusion (D*) and diffusion Kurtosis (K) coefficients were calculated from the NG-IVIM model. All patients underwent surgery. Tumor aggressiveness was defined at pathology. ADC and D may be used to distinguish tumors with and without aggressive features in tumor size between 1-2 cm.

Purpose

High-resolution neck ultrasonography (US) is now recommended and used in active surveillance for papillary thyroid carcinoma (PTC) patients (1-5). However, for PTCs with tumor size (1-2 cm), US has suboptimal sensitivity and specificity in the detection of aggressive features (6-8). Previous studies have shown that ADC (apparent diffusion coefficient) derived from DW-MRI was clinically relevant in assessing extrathyroidal extension in what appeared to be intrathyroidal papillary micro-carcinomas (tumor size <1cm) (9). In this study, a non-gaussian intravoxel incoherent motion (NG-IVIM) DW-MRI model developed in-house (10) was used to quantify diffusion and perfusion metrics to identify imaging biomarkers that preclude an active surveillance management approach for certain papillary thyroid cancers.

Methods

Patients and Multi-b value DW-MRI data acquisition: Our institutional review board approved this retrospective study and issued a waiver of informed consent. Twenty-four patients with PTC (age: 27-78 years, M/F: 8/16) were referred for a multi-b value DW-MRI study by physicians at our institution. All patients underwent pretreatment MRI on a GE 3T scanner with a 24-channel neurovascular phased-array coil prior to surgery. Multi-b value DW-MRI acquisitions were performed using a SS-EPI sequence (TR = 4000 ms, TE = minimum [ms], and 3 orthogonal directions) with b values of 0, 20, 50, 80, 200, 300, 500, 800, 1000, 1500 s/mm2, 4-8 slices of 5 mm thickness covering the tumor, FOV=20~24 cm, and acquisition matrix =128 × 128. Multi-b value DW-MRI data analysis: The regions of interest (ROI) on the tumor were placed by an experienced neuroradiologist. The ADC was calculated using the conventional mono-exponential model. The perfusion factor (f), diffusion coefficient (D), pseudo diffusion coefficient (D*) and diffusion Kurtosis coefficient (K) were calculated using the non-gaussian intravoxel incoherent motion model (NG-IVIM) developed in-house (10). Histopathologic examination: All patients underwent surgery after the MRI exams. The surgical specimen was reviewed by an experienced pathologist. Tumor aggressiveness was evaluated for each surgical specimen using standard histopathologic features (9). Ultrasonography measurements: US examinations were performed according to standard protocol that included grayscale and color Doppler US assessment of the thyroid bed and cervical lymph nodes in all neck compartments. Tumor size was defined as the largest diameter among the 3 dimensions provided. Statistical analysis: ADC, D, f, D* and K values among 2 different groups (i.e., tumors with aggressive features, tumors without aggressive features) were statistically analyzed to determine whether they significantly differed by using a Non-parametric Mann-Whitney U test. The ROC curve was used to assess the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. A p-value <0.05 was considered significant.

Results

Figure 1 shows MRI from a representative PTC patient with tumor aggressive features (female; 28y; max. tumor diameter, 2.1 cm). Tumors with aggressive features had significantly lower ADC and D values and higher f values than that of the tumor without tumor aggressive features (p<0.05) while K and D* were not significantly different for the 2 groups (Table 1). Using ROC analysis, the cutoff values of ADC, D and f that discriminates between PTCs with and without aggressive features were determined [ADC = 1.87 · 10–3 mm2/s, D = 1.93 · 10–3 mm2/s and f = 0.14] with a sensitivity, specificity and ROC curve area of 88.89%, 88.83%, and 0.84, respectively, for ADC, 88.89%, 88.83%, and 0.88, respectively, for D, and 88.89%, 66.67% and 0.78, respectively, for f (Figure 2). Therefore, ADC, D, and f were found to exhibit promise to be surrogate biomarkers for aggressiveness in PTC patients. For the treating Physician, to recommend active surveillance for tumors measuring 1-2 cm in size by US is very difficult as no data is available to justify this in PTC patients. Our results show that out of the 24 patients, 14 patients were in the critical size range and the ADC, and D were significantly different (Table 1) and able to differentiate between the 2 tumor types (p<0.05). Also, that K, D* and f metrics were not significantly different in this cohort (p>0.05). Therefore, offering new imaging metrics in conjunction with clinical data for counseling patients who are better suited for active surveillance.

Discussion and Conclusion

The magnitude of water diffusion reflects tissue micro-architecture while blood perfusion quantifies microcirculation in tumor tissues (10). Our study showed that ADC, and D may be used to distinguish tumors with and without aggressive features in tumor size ranging between 1-2 cm. ADC, and D exhibit their potential benefit in counseling PTC patients who may consider active surveillance and are not papillary micro-carcinomas (tumor size <1cm) on the onset.

Acknowledgements

Supported by NCI/NIH grant (R21CA176660-01A1)

References

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Figures

Figure 1. The representative PTC patient with tumor aggressive features (female; 28y; max. tumor diameter, 2.1 cm) (a) diffusion-weighted image (b = 0 s/mm2). (b) ADC map (x 10-3 mm2/s) overlaid on diffusion-weighted image (b = 0 s/mm2). (c) K map (x 10-3 mm2/s) overlaid on diffusion-weighted image (b = 0 s/mm2). (d) D* (x 10-3 mm2/s) map overlaid on diffusion-weighted image (b = 0 s/mm2). (e) D map (x 10-3 mm2/s) overlaid on diffusion-weighted image (b = 0 s/mm2). (f) f map overlaid on diffusion-weighted image (b = 0 s/mm2).

Figure 2. ROC curve to discriminate PTC patients with and without aggressive features using ADC (red line), D (green line), f (blue line), and US tumor size (brown line).

Table 1. Statistical analysis for the different metrics using tumor size by Ultrasonography.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)
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