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Purpose To report the feasibility, accuracy and initial clinical experience of the use of real-time magnetic resonance navigated ultrasound (rtMRnUS) in the surgical planning of breast-conserving surgery (BCS) via guide wire insertion. Materials and Methods 29 participants were recruited into this prospective ethics committee approved study. The first 4 cases were utilized as a training set. Participants underwent a supine contrast-enhanced breast MR examination with external fiducials and corresponding ink marks placed on the skin of the affected breast to act as co-registration pairs. MR examinations included both functional and morphological images. A LOGIQ E9 ultrasound system (GE Healthcare, Milwaukee, WI, USA) equipped with a 6 - 15 MHz transducer was utilized for rtMRnUS. To facilitate point co-registration of the previously acquired MR dataset with the real-time ultrasound, co-registration pairs were identified on both imaging modalities. The following co-registration quality metrics were recorded: root mean square deviation (RMSD), lesion and global accuracies. Post co-registration guide wire insertion was performed. Results Co-registration was successfully undertaken in all participants. Results from 25 participants are presented. The median (min, max) RMSD was 3.3 mm (0.6 mm, 8.8 mm). The global accuracy was assessed as very good (8), good (12), moderate (3) and poor (2) while the median (min, max) lesion accuracy was recorded at 8.9 mm (2.1 mm, 33.2 mm). Conclusion The use of rtMRnUS to facilitate guide wire insertion is a feasible technique. Generally, very good or good global registration can be expected. Lesion accuracy results indicate that a median difference, in 3 D space, of 9 mm can be expected between imaging modalities.

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PURPOSE: To evaluate diffusion weighted MRI (DW-MR) as a response metric for assessment of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer using prospective multi-center trials which provided MR scans along with clinical outcome information. MATERIALS AND METHODS: A total of 39 patients with locally advanced breast cancer accrued from three different prospective clinical trials underwent DW-MR examination prior to and at 3-7 days (Hull University), 8-11 days (University of Michigan) and 35 days (NeoCOMICE) post-treatment initiation. Thirteen patients, 12 of which participated in treatment response study, from UM underwent short interval (<1hr) MRI examinations, referred to as "test-retest" for examination of repeatability. To further evaluate stability in ADC measurements, a thermally controlled diffusion phantom was used to assess repeatability of diffusion measurements. MRI sequences included contrast-enhanced T1-weighted, when appropriate, and DW images acquired at b-values of 0 and 800 s/mm2. Histogram analysis and a voxel-based analytical technique, the Parametric Response Map (PRM), were used to derive diffusion response metrics for assessment of treatment response prediction. RESULTS: Mean tumor apparent diffusion coefficient (ADC) values generated from patient test-retest examinations were found to be very reproducible (|ΔADC|<0.1x10-3mm2/s). This data was used to calculate the 95% CI from the linear fit of tumor voxel ADC pairs of co-registered examinations (±0.45x10-3mm2/s) for PRM analysis of treatment response. Receiver operating characteristic analysis identified the PRM metric to be predictive of outcome at the 8-11 (AUC = 0.964, p = 0.01) and 35 day (AUC = 0.770, p = 0.05) time points (p<.05) while whole-tumor ADC changes where significant at the later 35 day time interval (AUC = 0.825, p = 0.02). CONCLUSION: This study demonstrates the feasibility of performing a prospective analysis of DW-MRI as a predictive biomarker of NAC in breast cancer patients. In addition, we provide experimental evidence supporting the use of sensitive analytical tools, such as PRM, for evaluating ADC measurements.

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PURPOSE: To determine if MRI data obtained at 3.0 T can more accurately report the size of DCIS as compared to radiographic mammography, as a whole cohort and when subdivided by lesion characteristics. METHODS: Thirty-nine participants underwent X-ray mammography and MRI prior to breast surgery for DCIS. Longest diameter (LD) measurements were recorded for each imaging modality and compared to histopathological LD via a logarithmic transformed Bland-Altman agreement plot methodology resulting in dimensionless mean difference and 95% limits of agreement (LoA). RESULTS: Data from 39 patients with a median age of 55 years (range 38-78 years) underwent analysis. Mastectomy was undertaken in 21 cases, while breast conserving surgery was performed in 18 subjects. Histopathological analysis revealed one low grade, nine intermediate grade, and 21 high grade lesions. The mean±standard deviation LD measurements for histopathology, X-ray mammography and MRI were 50.6±34.2 mm, 30.7±23.1 mm and 49.6±26.8 mm respectively. Bland-Altman agreement plot analysis for the whole cohort revealed not only a smaller logarithmic mean difference between MRI and histopathology (0.086), but also narrower 95% LoA (-0.941 to 1.113) compared with X-ray mammography and histopathology (mean difference -0.658, 95% LoA -3.503 to 2.187). When the level of agreement was assessed between clinically relevant subgroups additional significant differences were noted based on grade, hormonal receptor status, invasion, necrosis, mircocalcifications and growth pattern. CONCLUSION: MRI provides a more accurate estimation of DCIS size than X-ray mammography. MRI's superior ability was not only noted in general, but also for clinical relevant subdivisions such as grade and the presence or absence of necrosis.

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OBJECTIVES: To determine associations between dynamic contrast-enhanced MR imaging (DCE-MRI) parameters and survival intervals in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC), surgery, and adjuvant therapies. Further, to compare the prognostic value of DCE-MRI parameters against traditional survival indicators. METHODS: DCE-MRI and MR tumour volume measures were obtained prior to treatment and post 2nd NAC cycle. To demonstrate which parameters were associated with survival, Cox's proportional hazards models (CPHM) were employed. To avoid over-parameterisation, only those MR parameters with at least a borderline significant result were entered into the final CPHM. RESULTS: When considering disease-free survival positive axillary nodal status (hazard ratio [HR] 6.79), younger age (HR 3.37), negative oestrogen receptor status (HR 3.24), pre-treatment Maximum Enhancement Index (MaxEI) (HR 6.51), and percentage change in MaxEI (HR 1.02) represented the retained CPHM covariates. Similarly, positive axillary nodal status (HR 11.47), negative progesterone receptor status (HR 4.37) and percentage change in AUC90 (HR 1.01) represented the retained predictive variables for overall survival. CONCLUSIONS: Multivariate survival analysis has demonstrated that DCE-MRI parameters obtained prior to NAC and/or post 2nd cycle can provide independent prognostic information that can complement traditional prognostic indicators available prior to treatment. KEY POINTS: • MR-derived DCE-MRI parameters obtained prior to treatment have prognostic value. • Early treatment-induced reductions in DCE-MRI parameters represents a positive prognostic indicator. • DCE-MRI parameters provide independent prognostic information that can complement traditional prognostic indicators.

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Imaging biomarkers capable of early quantification of tumor response to therapy would provide an opportunity to individualize patient care. Image registration of longitudinal scans provides a method of detecting treatment associated changes within heterogeneous tumors by monitoring alterations in the quantitative value of individual voxels over time, which is unattainable by traditional volumetric-based histogram methods. The concepts involved in the use of image registration for tracking and quantifying breast cancer treatment response using parametric response mapping (PRM), a voxel-based analysis of diffusion-weighted magnetic resonance imaging (DW-MRI) scans, are presented. Application of PRM to breast tumor response detection is described, wherein robust registration solutions for tracking small changes in water diffusivity in breast tumors during therapy are required. Methodologies that employ simulations are presented for measuring expected statistical accuracy of PRM for response assessment. Test-retest clinical scans are used to yield estimates of system noise to indicate significant changes in voxel-based changes in water diffusivity. Overall, registration-based PRM image analysis provides significant opportunities for voxel-based image analysis to provide the required accuracy for early assessment of response to treatment in breast cancer patients receiving neoadjuvant chemotherapy.

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PURPOSE: There is little consensus regarding preoperative magnetic resonance imaging (MRI) in breast cancer (BC). We examined the association between preoperative MRI and local recurrence (LR) as primary outcome, as well as distant recurrence (DR), in patients with BC. METHODS: An individual person data (IPD) meta-analysis, based on preoperative MRI studies that met predefined eligibility criteria, was performed. Survival analysis (Cox proportional hazards modeling) was used to investigate time to recurrence and to estimate the hazard ratio (HR) for MRI. We modeled the univariable association between LR (or DR) and MRI, and covariates, and fitted multivariable models to estimate adjusted HRs. Sensitivity analysis was based on women who had breast conservation with radiotherapy. RESULTS: Four eligible studies contributed IPD on 3,180 affected breasts in 3,169 subjects (median age, 56.2 years). Eight-year LR-free survival did not differ between the MRI (97%) and no-MRI (95%) goups (P = .87), and the multivariable model showed no significant effect of MRI on LR-free survival: HR for MRI (versus no-MRI) was 0.88 (95% CI, 0.52 to 1.51; P = .65); age, margin status, and tumor grade were associated with LR-free survival (all P < .05). HR for MRI was 0.96 (95% CI, 0.52 to 1.77; P = .90) in sensitivity analysis. Eight-year DR-free survival did not differ between the MRI (89%) and no-MRI (93%) groups (P = .37), and the multivariable model showed no significant effect of MRI on DR-free survival: HR for MRI (v no-MRI) was 1.18 (95% CI, 0.76 to 2.27; P = .48) or 1.31 (95% CI, 0.76 to 2.27; P = .34) in sensitivity analysis. CONCLUSION: Preoperative MRI for staging the cancerous breast does not reduce the risk of LR or DR.

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As clinical features in struma ovarii patients in the absence of thyrotoxicosis are generally non-specific and resemble ovarian malignancy, preoperative radiological diagnosis becomes all the more relevant in order to avoid ovarian cancer type surgery (including bilateral salpingo-oophorectomy, hysterectomy, omentectomy and occasionally appendectomy) for this usually benign and rare ovarian mass. As struma ovarii is an uncommon entity, it is all the more important to perform state-of-the-art magnetic resonance (MR) imaging, including high-resolution imaging and diffusion-weighted imaging. The goal of this review paper is to give an update of the key findings of both benign and malignant struma ovarii and to present an unusual case of a purely cystic ovarian struma. Key Points • Clinical features in struma ovarii are generally non-specific and resemble ovarian malignancy.• Pre-operative radiological diagnosis is important to avoid ovarian cancer type surgery (bilateral salpingo-oophorectomy, hysterectomy, omentectomy and occasionally appendectomy).• State-of-the-art MR imaging might help to characterise this unusual ovarian mass.• Struma ovarii can occasionally present as a purely cystic lesion.• However, the role of imaging to identify struma ovarii preoperatively remains limited.

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OBJECTIVES: The ability to detect and identify malignant lesions within the prostate with conventional T2-weighted imaging is still limited. Although lesion conspicuity is improved with dynamic contrast-enhanced imaging there still remains some ambiguity as all tissues within the prostate may enhance. The aim of the current study was to take advantage of the improved signal-to-noise ratio at 3 T and assess the ability of 2 alternative pharmacokinetic models to clearly identify malignant areas within the prostate. We also aspire to assess the impact of tissue heterogeneity on variation in estimated pharmacokinetic parameters. MATERIALS AND METHODS: Quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the prostate was implemented using multiple flip angles for T1 determination, and a rapid dynamic 3D T1-weighted acquisition with parallel imaging and a temporal resolution of 6.7 s. Pharmacokinetic analysis was performed for regions of tumor, normal-appearing peripheral zone (PZ), and central gland (CG) using fast exchange limit (FXL) or fast exchange regimen (FXR) models. Cell density was obtained from hematoxylin and eosin stained whole mount radical prostatectomy specimens. RESULTS: Native tissue T1 was significantly lower in tumor and PZ tissue than in CG. The FXL model revealed increased mean K(trans), k(ep), and v(e) in tumor and CG compared with PZ. With the FXR model, fitting was improved and all parameters were significantly increased, however, there were no longer significant differences between regions for v(e). The additional parameter of the FXR model, tau(i), nominally representing mean lifetime of intracellular water, was significantly decreased in tumor compared with both PZ and CG. Rate constants for CG were significantly lower than those of tumor for both models. In addition, for all tissues, K(trans) and v(e) were positively correlated with cell density. CONCLUSIONS: Accounting for a finite water exchange rate between cells and their environment improves the discrimination of malignant from benign tissues within the prostate and may aid staging accuracy and ability to monitor response to treatment.

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OBJECTIVES: To assess the relationship between MRI derived parameters (apparent diffusion coefficient (ADC) and T2 relaxation time) and tumor cellularity as determined from whole mounted radical prostatectomy specimens, for both prostatic carcinoma and normal peripheral zone tissue. MATERIALS AND METHODS: Over a 16-month period, 20 patients (mean age: 61 years, range: 42-70 years) were prospectively recruited. Diffusion and T2 imaging were performed on a 3.0 Tesla scanner to enable subsequent ADC and T2 calculation. After radical retropubic prostatectomy specimens were whole-mounted and regions of interest (ROIs) drawn in areas of prostatic carcinoma and normal peripheral zone. Cell density was then determined using an adaptive histogram thresholding technique. Differences in tissue type were explored using the unpaired t test while the relationship between parameters was assessed using scatter-plots and the Pearson correlation coefficient. RESULTS: Significant differences (P < 0.0001 in all cases) were noted between peripheral zone tissue and prostatic carcinoma in terms of ADC (1.88 +/- 0.22 vs. 1.43 +/- 0.19 x 10(-3) mm2/s), T2 (142 +/- 24 vs. 109 +/- 20 milliseconds), and cell density (9.4% +/- 3.0% vs. 19.8% +/- 5.3%). A significant negative correlation with cell density was noted for both ADC (R = -0.695, P < 0.0001) and T2 (R = -0.505, P = 0.001). Trends for increased cell density, decreased ADC, and decreased T2 with increasing Gleason score were also noted. CONCLUSIONS: ADC and to a lesser extent T2 are good indicators of cell density. Because of the potential link with Gleason score, MRI derived parameters may have a prognostic role with regard to potential metastatic activity and tumor aggressiveness.

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Quantitative isotropic diffusion MRI and voxel-based analysis of the apparent diffusion coefficient (ADC) changes have been demonstrated to be able to accurately predict early response of brain tumors to therapy. The ADC value changes measured during pre- and posttherapy interval are closely correlated to treatment response. This work was demonstrated using a voxel-based analysis of ADC change during therapy in the brains of both rats and humans, following rigidly registering pre- and post-therapeutic ADC MRI exams. The primary goal of this paper is to extend this voxel-by-voxel analysis to assess therapeutic response in breast cancer. Nonlinear registration (with higher degrees of freedom) between the pre- and post-treatment exams is needed to ensure that the corresponding voxels actually contain similar cellular partial contributions due to soft tissue deformations in the breast and compartmental tumor changes during treatment as well. With limited data sets, we have observed the correlation between changes of ADC values and treatment response also exists in breast cancers. With diffusion scans acquired at three different timepoints (pre-treatment, early post-treatment and late post-treatment), we have also shown that ADC changes across responders within 5 weeks are a function of time interval after the initiation of treatment. Comparison of the experimental results with pathology shows that ADC changes can be used to evaluate early response of breast cancer treatment.

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The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

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Dynamic contrast-enhanced MRI (DCE-MRI) is an evolving tool for determining breast disease, which benefits from the move to imaging at 3 T. It has major capabilities for the diagnosis, detection and monitoring of malignancy. It benefits from being non-invasive and three-dimensional, allowing visualisation of the extent of disease and its angiogenic properties, visualisation of lesion heterogeneity, detection of changes in angiogenic properties before morphological alterations, and the potential to predict the overall response either before the start of therapy or early during treatment. In addition, DCE-MRI is emerging as a powerful tool for screening high-risk patients and for detecting high-grade ductal carcinoma in situ. However, there are also a number of limitations, including the overlap in enhancement patterns between malignant and benign disease, the failure to resolve microscopic disease particularly in the neoadjuvant setting, and the inconsistent predictive value of the enhancement pattern for clinical outcome. Careful consideration should be given to the technical requirements of individual examinations and the need for automation of post-processing techniques to appropriately handle the growing volume of data acquired. Research continues, focusing on the use of higher field strengths with improved spatial and temporal resolution data, improving understanding of the mechanism of contrast enhancement at the cellular level, and developing macromolecular and targeted contrast agents.

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The aim of this study was to investigate the utility of the water T(2) values of malignant breast lesions in predicting response after the first and second cycles of neoadjuvant chemotherapy (NAC), both alone and in combination with lesion volumes. Thirty-five patients were scanned before the commencement of chemotherapy and again after the first, second and final treatment cycles. Two methods of obtaining lesion T(2) were used: imaging, where a series of T(2)-weighted images was acquired (T(R)/T(E)=1000/30, 60, 90 and 120 ms), and spectroscopy, where the T(2) value of unsuppressed water signal was determined with a multiecho sequence (T(R)=1.5 s; initial T(E)=35 ms; 64 steps of 2.5 ms; 2 unsuppressed acquisitions per T(E)). Lesion volumes were computed from contrast-enhanced 3D fat-suppressed images. The study found that, using the imaging method of obtaining T(2), the ratio of the product of lesion T(2) and volume after the second cycle of NAC to pretreatment value is a good predictor of ultimate lesion response, defined as a > or =65% reduction in tumor volume after the final treatment cycle, with positive and negative predictive values of 95.5% and 84.6%, respectively.

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PURPOSE: To compare different imaging methods with single-voxel MR spectroscopy (MRS) for the quantification of fat content in phantoms at 3.0T. MATERIALS AND METHODS: Imaging and spectroscopy was performed on a GE Signa system. Eleven novel homogeneous fat-water phantoms were constructed with variation in fat content from 0% to 100%. These were imaged using three techniques and compared with single-voxel non-water-suppressed MRS. Pixel-by-pixel maps of fat fraction were produced and mean values compared to MRS-determined measurements. Preliminary in vivo examinations were subsequently performed in the breast and spine to compare the best imaging technique with MRS. RESULTS: All imaging methods significantly correlated with MRS (P < 0.001): IDEAL (r(2) = 0.985), IOP (r(2) = 0.888), WS (r(2) = 0.939), and FS (r(2) = 0.938). In addition, IDEAL provided artifact-free maps of fat fraction with superior uniformity. In vivo results using IDEAL produced values that were between 9% to 16% of the corresponding MRS values. CONCLUSION: This work demonstrates that imaging may be utilized as a high-resolution alternative to MRS for the quantification of fat content. In the future we intend to replace MRS with IDEAL in our clinical studies involving fat measurement.

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PURPOSE: To evaluate the efficacy of MR Spectroscopy (MRS) at 3.0 Tesla for the assessment of normal bone marrow composition and assess the variation in terms of age, gender, and skeletal site. MATERIALS AND METHODS: A total of 16 normal subjects (aged between eight and 57 years) were investigated on a 3.0 Tesla GE Signa system. To investigate axial and peripheral skeleton differences, non-water-suppressed spectra were acquired from single voxels in the calcaneus and lumbar spine. In addition, spectra were acquired at multiple vertebral bodies to assess variation within the lumbar spine. Data was also correlated with bone mineral density (BMD) measured in six subjects using dual-energy X-ray absorptiometry (DXA). RESULTS: Fat content was an order of magnitude greater in the heel compared to the spine. An age-related increase was demonstrated in the spine with values greater in men compared to female subjects. Significant trends in vertebral bodies within the same subjects were also shown, with fat content increasing L5 > L1. Population coefficient of variation (CV) was greater for fat fraction (FF) compared to BMD. CONCLUSION: Significant normal variations of marrow composition have been demonstrated, which provide important data for the future interpretation of patient investigations.

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CONTEXT: Octreotide causes significant tumour shrinkage in patients with acromegaly but the exact mechanism of action is unclear in vivo. OBJECTIVE: To determine the mechanism of action of octreotide in vivo using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DESIGN: Five patients with acromegaly were treated with octreotide as primary medical therapy. DCE-MRI was done at baseline and 24 weeks. Local ethical committee approval was granted. SETTING: Study was done in a tertiary care centre. PATIENTS: Five patients with newly diagnosed acromegaly were recruited. INTERVENTION: Patients were started on subcutaneous octreotide and DCE-MRI was done on 0 and 24 weeks. MAIN OUTCOME MEASURES: Amplitude of contrast intake, exchange rate and maximum enhancement index of tumour tissue was compared before and after treatment. RESULTS: Amplitude of contrast intake (9.87 +/- 3.52 vs. 4.97 +/- 1.96 P < or = 0.05) and exchange rate (6.27 +/- 1.57 vs. 1.63 +/- 0.76 P value < or = 0.01) were significantly higher at baseline in adenoma compared to normal pituitary tissue but was comparable to normal pituitary tissue after treatment. There was a significant decrease in amplitude of contrast intake and exchange rate which relates to functional vascularity of adenoma at 24 weeks compared to baseline (P-values 0.026 and 0.002 respectively) but there were no significant changes in the normal pituitary tissue. CONCLUSION: DCE-MRI in acromegalic tumours treated with octreotide showed a significant reduction in functional vascularity after octreotide therapy compared to baseline in pituitary adenomas. This supports the antiangiogenic action of somatostatin analogue therapy in vitro, but it remains unclear if this mechanism is important clinically in analogue pre-treatment reducing the effect of radiotherapy on these pituitary tumours.

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CONTEXT: Dopamine agonists (DA) may act on prolactinoma size and secretion through additional effects on adenoma vascularity that can be visualized using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). OBJECTIVE: We hypothesized that DAs may exert their effect through a change in tumour functional vascularity leading to a reduction of prolactin (PRL) levels and tumour size. SUBJECTS AND METHODS: To investigate this, 23 subjects were studied comprising five with macroprolactinomas, 11 with microprolactinomas, seven with non-lesion hyperprolactinemia and 15 normal volunteers (including five females on oral contraceptive pills). Patients with macroprolactinomas were treated with cabergoline 4 mg weekly and microprolactinomas were treated with quinagolide 75 microg daily for the duration of study. DCE-MRI was performed immediately pre-treatment and at 3-4 days, 1 and 3-4 months after treatment. Normal volunteers took three 75 microg quinagolide doses and were scanned pre-treatment and at 3 days. Data were analysed using the Brix model, producing a measure of vascular permeability and leakage space. RESULTS: PRL levels were significantly reduced in all patients and volunteers. Vascular parameters decreased significantly for four of five macroprolactinomas and all microprolactinomas which were maintained during the treatment period (p < 0.01). No changes were seen in normal volunteers or non-lesion hyperprolactinemia. One of five macroprolactinomas showed no change in either permeability or tumour size. CONCLUSION: Functional prolactinoma vascularity differs from non-lesion hyperprolactinemic pituitary and normal pituitary, and is responsive to DA therapy. The reduction in vascular parameters precedes shrinkage in macroprolactinomas, and if not seen within days of treatment may indicate DA resistance requiring early surgery.

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Echo-planar-based diffusion-weighted imaging (DWI) of the prostate is increasingly being suggested as a viable technique, complementing information derived from conventional magnetic resonance imaging methods for use in tissue discrimination. DWI has also been suggested as a potentially useful tool in the assessment of tumor response to treatment. In this study, the repeatability of apparent diffusion coefficient (ADC) values obtained from both DWI and diffusion tensor imaging (DTI) has been assessed as a precursor to determining the magnitude of treatment-induced changes required for reliable detection. The repeatability values of DWI and DTI were found to be similar, with ADC values repeatable to within 35% or less over a short time period of a few minutes and a longer time period of a month. Fractional anisotropy measurements were found to be less repeatable (between 26% and 71%), and any changes duly recorded in longitudinal studies must therefore be treated with a degree of caution.

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Traditionally, tumor response has been assessed via tumor size measurements during the course of a treatment. However, changes in these morphologically based measures occur relatively late in the course of a treatment. Alternative biomarkers are currently being evaluated to enable an earlier assessment of treatment to facilitate early cessation and cost savings. Diffusion-weighted imaging (DWI) has been identified by preclinical studies to be a likely alternative to tumor size measurements. In this study, 10 patients were examined prior to and after the first and second chemotherapy cycle time points. Longest diameter tumor measurements and apparent diffusion coefficients (ADCs) were recorded at each exam. An increase in the mean (normalized) ADC was noted as early as the first cycle time point. However, a reduction in the mean (normalized) longest diameter was only noted at the second cycle time point. Significant alterations from the baseline value were noted for ADC at the first (P=.005) and second cycle time points (P=.004). Longest diameter measurements only achieved a borderline significance at the second time point (P=.057). These results indicate that DWI may provide a suitable biomarker capable of providing an indication of response to treatment prior to tumor size measurements.

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