Maria A. Schmidt

Evaluation of magnetic resonance diffusion and spectroscopy measurements as predictive biomarkers in stage 1 cervical cancer

OBJECTIVE To establish whether ADC and total choline were significantly different between cervical tumors with different histological characteristics (type, degree of differentiation, presence or absence of lymphovascular invasion, lymph-node involvement) in order to establish their role as predictive biomarkers. METHODS 62 patients with stage 1 cervical cancer were scanned at 1.5 T. T2-weighted imaging (TR/TE=4500/80 ms), to identify tumor and normal cervix, was followed by diffusion-weighted imaging (TR/TE=2500/69 ms; 5 b-values 0, 100, 300, 500 and 800 s/mm(2)) and MR spectroscopic imaging (15 mm slice, 7.5 mm in-plane resolution, TR=888 ms). Regions of interest in normal cervix and tumor were drawn on apparent diffusion coefficient (ADC) maps by an expert observer with reference to the T2-weighted images. ADCs were calculated using a monoexponential fit of data from all b-values. MR spectra in voxels designated as tumor (>30% tumor) or non-tumor were quantified using LCModel and referenced to tissue water. RESULTS There was a statistically significant difference between the ADC of tumor regions (1117+/-183x10(-6) mm(2)/s) and of selected normal regions (1724+/-198x10(-6) mm(2)/s; p<0.001), and between tumors that were well/moderately differentiated (1196+/-181x10(-6) mm(2)/s) compared with those that were poorly differentiated (1038+/-153x10(-6) mm(2)/s; p=0.016). There was no significant difference between the ADCs of the tumors when separated by other characteristics (tumor type, lymphovascular invasion, lymph-node metastases), or between measured total choline in any of the groups. CONCLUSION ADCs are lower in cancer compared to normal cervical tissue, with degree of tumor differentiation contributing to this difference.

Radiotherapy planning using MRI.

The use of magnetic resonance imaging (MRI) in radiotherapy (RT) planning is rapidly expanding. We review the wide range of image contrast mechanisms available to MRI and the way they are exploited for RT planning. However a number of challenges are also considered: the requirements that MR images are acquired in the RT treatment position, that they are geometrically accurate, that effects of patient motion during the scan are minimized, that tissue markers are clearly demonstrated, that an estimate of electron density can be obtained. These issues are discussed in detail, prior to the consideration of a number of specific clinical applications. This is followed by a brief discussion on the development of real-time MRI-guided RT.

The value of magnetic resonance imaging in target volume delineation of base of tongue tumours--a study using flexible surface coils.

INTRODUCTION Magnetic resonance imaging (MRI) provides superior diagnostic accuracy over computed tomography (CT) in oropharyngeal tumours. Precise delineation of the gross tumour volume (GTV) is mandatory in radiotherapy planning when a GTV boost is required. CT volume definition in this regard is poor. We studied the feasibility of using flexible surface (flex-L) coils to obtain MR images for MR-CT fusion to assess the benefit of MRI over CT alone in planning base of tongue tumours. METHODS Eight patients underwent CT and MRI radiotherapy planning scans with an immobilisation device. Distortion-corrected T1-weighted post-contrast MR scans were fused to contrast-enhanced planning CT scans. GTV, clinical target and planning target volumes (CTV, PTV) and organs at risk (OAR) were delineated on CT, then on MRI with blinding to the CT images. The volumetric and spatial differences between MRI and CT volumes for GTV, CTV, PTV and OAR were compared. MR image distortions due to field inhomogeneity and non-linear gradients were corrected and the need for such correction was evaluated. RESULTS The mean primary GTV was larger on MRI (22.2 vs. 9.5 cm(3), p=0.05) than CT. The mean primary and nodal GTV (i.e. BOT and macroscopic nodes) was significantly larger on MRI (27.2 vs. 14.4 cm(3), p=0.05). The volume overlap index (VOI) between MRI and CT for the primary was 0.34 suggesting that MRI depicts parts of the primary tumour not detected by CT. There was no significant difference in volume delineation between MR and CT for CTV, PTV, nodal CTV and nodal PTV. MRI volumes for brainstem and spinal cord were significantly smaller due to improved organ definition (p=0.002). Susceptibility and gradient-related distortions were not found to be clinically significant. CONCLUSION MRI improves the definition of tongue base tumours and neurological structures. The use of MRI is recommended for GTV dose-escalation techniques to provide precise depiction of GTV and improved sparing of spinal cord and brainstem.

Tumor Bed Delineation for Partial Breast and Breast Boost Radiotherapy Planned in the Prone Position: What Does MRI Add to X-ray CT Localization of Titanium Clips Placed in the Excision Cavity Wall?

PURPOSE To compare tumor bed (TB) volumes delineated using magnetic resonance imaging plus computed tomography and clips (MRCT) with those delineated using CT and clips (CT/clips) alone in postlumpectomy breast cancer patients positioned prone and to determine the value of MRCT for planning partial breast irradiation (PBI). METHODS AND MATERIALS Thirty women with breast cancer each had 6 to 12 titanium clips secured in the excision cavity walls at lumpectomy. Patients underwent CT imaging in the prone position, followed by MRI (T(1)-weighted [standard and fat-suppressed] and T(2)-weighted sequences) in the prone position. TB volumes were delineated separately on CT and on fused MRCT datasets. Clinical target volumes (CTV) (where CTV = TB + 15 mm) and planning target volumes (PTV) (where PTV = CTV + 10 mm) were generated. Conformity indices between CT- and MRCT-defined target volumes were calculated (ratio of the volume of agreement to total delineated volume). Discordance was expressed as a geographical miss index (GMI) (where the GMI = the fraction of total delineated volume not defined by CT) and a normal tissue index (the fraction of total delineated volume designated as normal tissue on MRCT). PBI dose distributions were generated to cover CT-defined CTV (CTV(CT)) with >or=95% of the reference dose. The percentage of MRCT-defined CTV (CTV(MRCT)) receiving >or=95% of the reference dose was measured. RESULTS Mean conformity indices were 0.54 (TB), 0.84 (CTV), and 0.89 (PTV). For TB volumes, the GMI was 0.37, and the NTI was 0.09. Median percentage volume coverage of CTV(CT) was 97.1% (range, 95.3%-100.0%) and of CTV(MRCT) was 96.5% (range, 89.0%-100.0%). CONCLUSIONS Addition of MR to CT/clip data generated TB volumes that were discordant with those based on CT/clips alone. However, clinically satisfactory coverage of CTV(MRCT) by CTV(CT)-based tangential PBI fields provides support for CT/clip-based TB delineation remaining the method of choice for PBI/breast boost radiotherapy planned using tangential fields.

Changes in functional imaging parameters following induction chemotherapy have important implications for individualised patient-based treatment regimens for advanced head and neck cancer

BACKGROUND When induction chemotherapy (IC) is used prior to chemoradiotherapy (CRT) in head and neck cancer (HNC), functional imaging (FI) may inform adaptation of treatment plans with the aim of optimising outcomes. Understanding the impact of IC on FI parameters is, therefore, essential. PURPOSE To prospectively evaluate the feasibility of acquiring serial FI ((18)F-FDG-PET, diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI) and its role in defining individualised treatment regimens following IC in HNC. METHODS AND MATERIALS Ten patients with stage III and IV HNC underwent conventional (CT and MRI) and functional (DW, DCE-MRI and (18)F-FDG-PET/CT) imaging at baseline and following two cycles of IC prior to definitive CRT. RESULTS One patient withdrew due to claustrophobia. Seven out of nine patients had a complete metabolic response to IC on (18)F-FDG-PET imaging. DCE-MRI showed a significant fall in transfer constant (K(trans)) (0.209 vs 0.129 min(-1)P<0.01) and integrated area under gadolinium curve at 60s (IAUGC6O) (18.4 vs 11.9 mmol/min, P<0.01) and DW-MRI a rise in ADC (0.89 vs 1.06 × 10(-3) mm(2)/s, P<0.01) following IC. CONCLUSIONS Acquiring FI sequences is feasible in HNC. There are marked changes in FI parameters following IC which may guide adaptation of individualised treatment regimens.

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T

To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.

Evaluation of diffusion models in breast cancer

PURPOSE The purpose of this study is to investigate whether the microvascular pseudodiffusion effects resulting with non-monoexponential behavior are present in breast cancer, taking into account tumor spatial heterogeneity. Additionally, methodological factors affecting the signal in low and high diffusion-sensitizing gradient ranges were explored in phantom studies. METHODS The effect of eddy currents and accuracy of b-value determination using a multiple b-value diffusion-weighted MR imaging sequence were investigated in test objects. Diffusion model selection and noise were then investigated in volunteers (n = 5) and breast tumor patients (n = 21) using the Bayesian information criterion. RESULTS 54.3% of lesion voxels were best fitted by a monoexponential, 26.2% by a stretched-exponential, and 19.5% by a biexponential intravoxel incoherent motion (IVIM) model. High correlation (0.92) was observed between diffusion coefficients calculated using mono- and stretched-exponential models and moderate (0.59) between monoexponential and IVIM (medians: 0.96/0.84/0.72 × 10(-3) mm(2)/s, respectively). Distortion due to eddy currents depended on the direction of the diffusion gradient and displacement varied between 1 and 6 mm for high b-value images. Shift in the apparent diffusion coefficient due to intrinsic field gradients was compensated for by averaging diffusion data obtained from opposite directions. CONCLUSIONS Pseudodiffusion and intravoxel heterogeneity effects were not observed in approximately half of breast cancer and normal tissue voxels. This result indicates that stretched and IVIM models should be utilized in regional analysis rather than global tumor assessment. Cross terms between diffusion-sensitization gradients and other imaging or susceptibility-related gradients are relevant in clinical protocols, supporting the use of geometric averaging of diffusion-weighted images acquired with diffusion-sensitization gradients in opposite directions.

Consensus opinion on MRI simulation for external beam radiation treatment planning

AIM To determine the levels at which consensus could be reached regarding general and site-specific principles of MRI simulation for offline MRI-aided external beam radiation treatment planning. METHODS A process inspired by the Delphi method was employed to determine levels of consensus using a series of questionnaires interspersed with controlled opinion feedback. RESULTS In general, full consensus was reached regarding general principles of MRI simulation. However, the level of consensus decreased when site-specific principles of MRI simulation were considered. CONCLUSIONS These results indicate variability in MRI simulation approaches that are largely explained by the use of MRI in combination with CT.

Quantitative Contrast-Enhanced Magnetic Resonance Lymphangiography of the Upper Limbs in Breast Cancer Related Lymphedema: An Exploratory Study

Abstract Background: Contrast-Enhanced Magnetic Resonance Lymphangiography (CE-MRL) presents some limitations: (i) it does not quantify lymphatic functionality; and (ii) enhancement of vascular structures may confound image interpretation. Furthermore, although CE-MRL is well described in the published literature for the lower limbs, there is a paucity of data with regards to its use in the upper limbs. In this proof-of-principle study, we propose a new protocol to perform CE-MRL in the upper limbs of patients with breast cancer-related lymphedema (BCRL) which addresses these limitations. Methods and Results: CE-MRL was performed using a previously published (morphological) protocol and the proposed protocol (quantitative) on both the ipsilateral (abnormal) and contralateral (normal) arms of patients with BCRL. The quantitative protocol employs contrast agent (CA) intradermal injections at a lower concentration to prevent T2*-related signal decay. Both protocols provided high-resolution three-dimensional images of upper limb lymphatic vessels. CA uptake curves were utilized to distinguish between lymphatic vessels and vascular structures. The quantitative protocol minimized venous enhancement and avoided spurious delays in lymphatic enhancement due to short T2* values, enabling correct CA uptake characterization. The quantitative protocol was therefore employed to measure the lymphatic fluid velocity, which demonstrated functional differences between abnormal and normal arms. The velocity values were in agreement with previously reported lymphoscintigraphy and near infra-red lymphangiography measurements. Conclusions: This work demonstrated the feasibility of CE-MRL of the upper limbs in patients with BRCL, introducing an advanced imaging and analysis protocol suitable for anatomical and functional study of the lymphatic system.

Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique

Background:Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its sensitivity/specificity, document tumour-to-stromal contrast and establish the effect of imaging on surgical management.Methods:Following ethical approval and written informed consent, 57 consecutive patients with suspected stage Ia/Ib1 cervical cancer underwent evMRI at 3.0-T using T2-W and ZOOM-DWI. Sensitivity/specificity were calculated against histopathology for two independent observers. Tumour-to-stromal contrast was determined on T2-W, and diffusion-weighted (b=800 s mm−2) images and apparent diffusion coefficients (ADCs) were recorded. In patients due for radical vaginal trachelectomy (RVT), change of surgical management based on imaging findings was documented.Results:Sensitivity/specificity for detecting tumour was the following: reporting read 88.0/81.8%, anonymised read 92.0/81.8% (observer 1); 84.0/72.7% (observer2; median tumour volume=1.7 cm3). Intraobserver agreement was excellent (kappa=0.89) and the interobserver agreement was good (kappa=0.65). Tumour-to-stromal contrast was greater on ZOOM-DWI compared with T2-W images (3.35±2.36 vs 1.39±0.95; P<0.0004). Tumour and stromal ADCs were significantly different (P<0.00001). In 31 patients due for RVT, evMRI altered surgical management in 12 (38.7%) cases (10 cone-biopsy, 2 chemoradiotherapy).Conclusion:T2-W+ZOOM-DWI evMRI has high sensitivity/specificity for detecting stage Ia/Ib1 cervical tumours; in patients due for RVT, the surgical management was altered in ∼39%.