Parallel transmit hybrid pulse design for controlled on-resonance magnetization transfer in R1 mapping at 7T.

PURPOSE: This work proposes a "hybrid" RF pulse design method for parallel transmit (pTx) systems to simultaneously control flip angle and root-mean-squared B 1 + $$ {\mathrm{B}}_1^{+} $$ ( B 1 rms $$ {B}_1^{\mathrm{rms}} $$ ). These pulses are generally only designed for flip angle, however, this can lead to uncontrolled B 1 rms $$ {B}_1^{\mathrm{rms}} $$ , which then leads to variable magnetization transfer (MT) effects. We demonstrate the hybrid design approach for quantitative imaging where both flip angle and B 1 rms $$ {B}_1^{\mathrm{rms}} $$ are important. THEORY AND METHODS: A dual cost function optimization is performed containing the normalized mean squared errors of the flip angle and B 1 rms $$ {B}_1^{\mathrm{rms}} $$ distributions weighted by a parameter λ $$ \lambda $$ . Simulations were conducted to study the behavior of both properties when simultaneously optimizing them. In vivo experiments on a 7T MRI system with an 8-channel pTx head coil were carried out to study the effect of the hybrid design approach on variable flip angle R 1 $$ {\mathrm{R}}_1 $$ (= 1/T1) mapping. RESULTS: Simulations showed that both flip angle and B 1 rms $$ {B}_1^{\mathrm{rms}} $$ can be homogenized simultaneously without detriment to either when compared to an individual optimization. By homogenizing flip angle and B 1 rms $$ {B}_1^{\mathrm{rms}} $$ , R 1 $$ {\mathrm{R}}_1 $$ maps were more uniform (coefficient of variation 6.6% vs. 13.0%) compared to those acquired with pulses that only homogenized flip angle. CONCLUSION: The proposed hybrid design homogenizes on-resonance MT effects while homogenizing the flip angle distribution, with only a small detriment in the latter compared to a pulse that just homogenizes flip angle. This improved R 1 $$ {\mathrm{R}}_1 $$ mapping by controlling incidental MT effects, yielding more uniform R 1 $$ {\mathrm{R}}_1 $$ maps.

Simultaneous Optimization of MP2RAGE T1 -weighted (UNI) and FLuid And White matter Suppression (FLAWS) brain images at 7T using Extended Phase Graph (EPG) Simulations.

PURPOSE: The MP2RAGE sequence is typically optimized for either T1 -weighted uniform image (UNI) or gray matter-dominant fluid and white matter suppression (FLAWS) contrast images. Here, the purpose was to optimize an MP2RAGE protocol at 7 Tesla to provide UNI and FLAWS images simultaneously in a clinically applicable acquisition time at <0.7 mm isotropic resolution. METHODS: Using the extended phase graph formalism, the signal evolution of the MP2RAGE sequence was simulated incorporating T2 relaxation, diffusion, RF spoiling, and B1 + variability. Flip angles and TI were optimized at different TRs (TRMP2RAGE ) to produce an optimal contrast-to-noise ratio for UNI and FLAWS images. Simulation results were validated by comparison to MP2RAGE brain scans of 5 healthy subjects, and a final protocol at TRMP2RAGE  = 4000 ms was applied in 19 subjects aged 8-62 years with and without epilepsy. RESULTS: FLAWS contrast images could be obtained while maintaining >85% of the optimal UNI contrast-to-noise ratio. Using TI1 /TI2 /TRMP2RAGE of 650/2280/4000 ms, 6/8 partial Fourier in the inner phase-encoding direction, and GRAPPA factor = 4 in the other, images with 0.65 mm isotropic resolution were produced in <7.5 min. The contrast-to-noise ratio was around 20% smaller at TRMP2RAGE  = 4000 ms compared to that at TRMP2RAGE  = 5000 ms; however, the 20% shorter duration makes TRMP2RAGE  = 4000 ms a good candidate for clinical applications example, pediatrics. CONCLUSION: FLAWS and UNI images could be obtained in a single scan with 0.65 mm isotropic resolution, providing a set of high-contrast images and full brain coverage in a clinically applicable scan time. Images with excellent anatomical detail were demonstrated over a wide age range using the optimized parameter set.

Parallel transmit pulse design for saturation homogeneity (PUSH) for magnetization transfer imaging at 7T.

PURPOSE: This work proposes a novel RF pulse design for parallel transmit (pTx) systems to obtain uniform saturation of semisolid magnetization for magnetization transfer (MT) contrast in the presence of transmit field B1+ inhomogeneities. The semisolid magnetization is usually modeled as being purely longitudinal, with the applied B1+ field saturating but not rotating its magnetization; thus, standard pTx pulse design methods do not apply. THEORY AND METHODS: Pulse design for saturation homogeneity (PUSH) optimizes pTx RF pulses by considering uniformity of root-mean squared B1+ , B1rms , which relates to the rate of semisolid saturation. Here we considered designs consisting of a small number of spatially non-selective sub-pulses optimized over either a single 2D plane or 3D. Simulations and in vivo experiments on a 7T Terra system with an 8-TX Nova head coil in five subjects were carried out to study the homogenization of B1rms and of the MT contrast by acquiring MT ratio maps. RESULTS: Simulations and in vivo experiments showed up to six and two times more uniform B1rms compared to circular polarized (CP) mode for 2D and 3D optimizations, respectively. This translated into 4 and 1.25 times more uniform MT contrast, consistently for all subjects, where two sub-pulses were enough for the implementation and coil used. CONCLUSION: The proposed PUSH method obtains more uniform and higher MT contrast than CP mode within the same specific absorption rate (SAR) budget.

Quantitative prediction of the extent of pelvic tumour ablation by magnetic resonance-guided high intensity focused ultrasound.

BACKGROUND: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) therapy of pelvic tumors is currently assessed by visual estimation of the proportion of tumor that can be reached by the device's focus (coverage). Since it is important to assess whether enough energy reaches the tumor to achieve ablation, a methodology for estimating the proportion of the tumor that can be ablated (treatability) was developed. Predicted treatability was compared against clinically achieved thermal ablation. METHODS: MR Dixon sequence images of five patients with recurrent gynecological tumors were acquired during their treatment. Acousto-thermal simulations were performed using k-Wave for three exposure points (the deepest and shallowest reachable focal points within the tumor, identified from tumor coverage analysis, and a point halfway in-between) per patient. Interpolation between the resulting simulated ablated tissue volumes was used to estimate the maximum treatable depth and hence, tumor treatability. Predicted treatability was compared both to predicted tumor coverage and to the clinically treated tumor volume. The intended and simulated volumes and positions of ablated tissues were compared. RESULTS: Predicted treatability was less than coverage by 52% (range: 31-78%) of the tumor volume. Predicted and clinical treatability differed by 9% (range: 1-25%) of tumor volume. Ablated tissue volume and position varied with beam path length through tissue. CONCLUSION: Tumor coverage overestimated patient suitability for MRgHIFU therapy. Employing patient-specific simulations improved treatability assessment. Patient treatability assessment using simulations is feasible.

Feasibility of palliating recurrent gynecological tumors with MRGHIFU: comparison of symptom, quality-of-life, and imaging response in intra and extra-pelvic disease.

OBJECTIVE: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions. METHODS: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors. RESULTS: Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intra-pelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. CONCLUSION: MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.

Prediction of pelvic tumour coverage by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) from referral imaging.

BACKGROUND: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a 'best-guess' treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging. METHODS: The algorithm was developed from volunteer images and tested with patient data. MR images were acquired for five healthy volunteers and five patients with recurrent gynaecological cancer. Subjects were MR imaged supine and in oblique-supine-decubitus MRgHIFU treatment positions. Body outline and bones were segmented for all subjects, with organs-at-risk and tumors also segmented for patients. Supine images were aligned with treatment images to simulate a treatment dataset. Target coverage (of patient tumors and volunteer intra-pelvic soft tissue), i.e. the volume reachable by the MRgHIFU focus, was quantified. Target coverage predicted from supine imaging was compared to that from treatment imaging. RESULTS: Mean (±standard deviation) absolute difference between supine-predicted and treatment-predicted coverage for 5 volunteers was 9 ± 6% (range: 2-22%) and for 4 patients, was 12 ± 7% (range: 4-21%), excluding a patient with poor acoustic coupling (coverage difference was 53%). CONCLUSION: Prediction of MRgHIFU target coverage from referral imaging appears feasible, facilitating further development of automated evaluation of patient suitability for MRgHIFU.

Comparison of Imaging Changes and Pain Responses in Patients with Intra- or Extraosseous Bone Metastases Treated Palliatively with Magnetic Resonance-Guided High-Intensity-Focused Ultrasound.

PURPOSE: This study compared changes in imaging and in pain relief between patients with intraosseous, as opposed to extraosseous bone metastases. Both groups were treated palliatively with magnetic resonance-guided high-intensity-focused ultrasound (MRgHIFU). MATERIALS AND METHODS: A total of 21 patients were treated prospectively with MRgHIFU at 3 centers. Intraprocedural thermal changes measured using proton resonance frequency shift (PRFS) thermometry and gadolinium-enhanced T1-weighted (Gd-T1W) image appearances after treatment were compared for intra- and extraosseous metastases. Pain scores and use of analgesic therapy documented before and up to 90 days after treatment were used to classify responses and were compared between the intra- and extraosseous groups. Gd-T1W changes were compared between responders and nonresponders in each group. RESULTS: Thermal dose volumes were significantly larger in the extraosseous group (P = 0.039). Tumor diameter did not change after treatment in either group. At day 30, Gd-T1W images showed focal nonenhancement in 7 of 9 patients with intraosseous tumors; in patients with extraosseous tumors, changes were heterogeneous. Cohort reductions in worst-pain scores were seen for both groups, but differences from baseline at days 14, 30, 60, and 90 were only significant for the intraosseous group (P = 0.027, P = 0.013, P = 0.012, and P = 0.027, respectively). By day 30, 67% of patients (6 of 9) with intraosseous tumors were classified as responders, and the rate was 33% (4 of 12) for patients with extraosseous tumors. In neither group was pain response indicated by nonenhancement on Gd-T1W. CONCLUSIONS: Intraosseous tumors showed focal nonenhancement by day 30, and patients had better pain response to MRgHIFU than those with extraosseous tumors. In this small cohort, post-treatment imaging was not informative of treatment efficacy.

Distortion correction of echo-planar diffusion-weighted images of uterine cervix.

PURPOSE: To investigate the clinical utility of the reverse gradient algorithm in correcting distortions in diffusion-weighted images of the cervix and for increasing diagnostic performance. MATERIALS AND METHODS: Forty-one patients ages 25-72 years (mean 40 ± 11 years) with suspected or early stage cervical cancer were imaged at 3T using an endovaginal coil. T2 -weighted (W) and diffusion-weighted images with right and left phase-encode gradient directions were obtained coronal to the cervix (b = 0, 100, 300, 500, 800 s mm(-2) ). Differences in angle of the endocervical canal to the x-axis between T2 W and right-gradient, left-gradient, and corrected images were measured. Uncorrected and corrected images were assessed for diagnostic performance when viewed together with T2 W images by two independent observers against subsequent histology. RESULTS: The angles of the endocervical canal relative to the x-axis were significantly different between the T2 W images and the right-gradient images (P = 0.007), approached significance for left-gradient images (P = 0.055), and were not significantly different after correction (P = 0.95). Corrected images enabled a definitive diagnosis in 34% (n = 14) of patients classified as equivocal on uncorrected images. Tumor volume in this subset was 0.18 ± 0.44 cm(3) (mean ± SD; sensitivity of detection 100% [8/8], specificity 50% [3/6] for an experienced observer). Correction did not improve diagnostic performance for the less-experienced observer. CONCLUSION: Distortion-corrected diffusion-weighted images improved correspondence with T2 W images and diagnostic performance in a third of cases.

Comparison of optimised endovaginal vs external array coil T2-weighted and diffusion-weighted imaging techniques for detecting suspected early stage (IA/IB1) uterine cervical cancer.

OBJECTIVE: To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours. METHODS: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement. RESULTS: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively). CONCLUSION: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging. KEY POINTS: • Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. • Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. • Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.

Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma. MATERIALS AND METHODS: This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response. RESULTS: Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001). CONCLUSION: Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma.

Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma.

31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi) using the chemical shift difference between pH-dependent inorganic phosphate (Pi) and a pH-independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct Pi­PCr method was best for those spectra with a very well-defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the Pi­αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water-based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the Pi­αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment-related changes of the order of 0.1 pH units should be detectable.

Preoperative imaging in patients undergoing trachelectomy for cervical cancer: validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T.

AIM: The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy. PATIENTS/INTERVENTIONS: 55 consecutive patients 25-44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded. RESULTS: Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm(3), IQR=0.14-1.06 cm(3)). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer 1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer 2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size correlated between each observer and histology (observer 1 r=0.91, p<0.0001; observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer 2: r=0.21, p=0.16); however, differences between observer measurements and histology were not significant (size p=0.09, volume p=0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p=0.1 both observers). CONCLUSION: In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

OBJECTIVE: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

High resolution and contrast 7 tesla MR brain imaging of the neonate.

Introduction: Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system. Methods: Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM). Results: There was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy. Discussion: We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.

Diffusion weighted imaging of the normal breast: reproducibility of apparent diffusion coefficient measurements and variation with menstrual cycle and menopausal status.

OBJECTIVES: To establish the reproducibility of apparent diffusion coefficient (ADC) measurements in normal fibroglandular breast tissue and to assess variation in ADC values with phase of the menstrual cycle and menopausal status. METHODS: Thirty-one volunteers (13 premenopausal, 18 postmenopausal) underwent magnetic resonance twice (interval 11-22 days) using diffusion-weighted MRI. ADC(total) and a perfusion-insensitive ADC(high) (omitting b = 0) were calculated. Reproducibility and inter-observer variability of mean ADC values were assessed. The difference in mean ADC values between the two phases of the menstrual cycle and the postmenopausal breast were evaluated. RESULTS: ADC(total) and ADC(high) showed good reproducibility (r% = 17.6, 22.4). ADC(high) showed very good inter-observer agreement (kappa = 0.83). The intraclass correlation coefficients (ICC) were 0.93 and 0.91. Mean ADC values were significantly lower in the postmenopausal breast (ADC(total) 1.46 ± 0.3 × 10(-3) mm(2)/s, ADC(high) 1.33 ± 0.3 × 10(-3) mm(2)/s) compared with the premenopausal breast (ADC(total) 1.84 ± 0.26 × 10(-3) mm(2)/s, ADC(high) 1.77 ± 0.26 × 10(-3) mm(2)/s; both P < 0.001). No significant difference was seen in ADC values in relation to menstrual cycle (ADC(total) P = 0.2, ADC(high) P = 0.24) or between postmenopausal women taking or not taking oestrogen supplements (ADC(total) P = 0.6, ADC(high) P = 0.46). CONCLUSIONS: ADC values in fibroglandular breast tissue are reproducible. Lower ADC values within the postmenopausal breast may reduce diffusion-weighted contrast and have implications for accurately detecting tumours. KEY POINTS: • ADC values from fibroglandular breast tissue are measured reproducibly by multiple observers. • Mean ADC values were significantly lower in postmenopausal than premenopausal breast tissue. • Mean ADC values did not vary significantly with menstrual cycle. • Low postmenopausal ADC values may hinder tumour detection on DW-MRI.

Diffusion-weighted MRI for locally recurrent prostate cancer after external beam radiotherapy.

OBJECTIVE: The objectives of our study were to establish the apparent diffusion coefficients (ADCs) of tumor and nontumor irradiated tissues in patients with suspected postradiation recurrence of prostate cancer and to determine the sensitivity and specificity of a combination of T2-weighted and diffusion-weighted imaging (DWI) for detecting local recurrence. MATERIALS AND METHODS: Twenty-four patients with rising prostate-specific antigen levels after having completed radiation therapy 30-130 months earlier (median, 62 months) underwent endorectal T2-weighted imaging and DWI (b = 0, 100, 300, 500, and 800 s/mm(2)) followed by transrectal ultrasound (TRUS)-guided biopsy. Images were scored prospectively as positive for tumor if a region of low signal intensity on T2-weighted imaging within the prostate corresponded with a focally restricted area on the ADC map. A region of interest (ROI) was drawn around the suspicious lesion on a single slice of the ADC map and a corresponding ROI was drawn around presumed nontumor irradiated peripheral zone and central gland tissues on the opposite side of the prostate. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined against TRUS-guided biopsy reference standard (octant, n = 17; sextant, n = 5; two samples, n = 1; 12 samples, n = 1). RESULTS: Sixteen of 24 patients (66.7%) had positive histology findings. The median tumor ROI area was 0.37 cm(2) (quartiles, 0.30 and 0.82 cm(2)). The sensitivity, specificity, PPV, and NPV for detecting tumor were 93.8%, 75%, 88.2%, and 85.7%, respectively. A cutoff ADC of 1216 × 10(-6) mm(2)/s could predict tumor with 100% sensitivity and 96% specificity (area under the receiver operating characteristic curve = 0.992). CONCLUSION: An ADC derived from DWI is a useful adjunct to T2-weighted MRI for detecting local tumor recurrence larger than 0.4 cm(2) within the prostate.

Metastatic ovarian and primary peritoneal cancer: assessing chemotherapy response with diffusion-weighted MR imaging--value of histogram analysis of apparent diffusion coefficients.

PURPOSE: To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer. MATERIALS AND METHODS: Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis. RESULTS: Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P < .001), while skew and kurtosis decreased after the third (P < .001 and P = .006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy. CONCLUSION: An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer.

Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2- and diffusion-weighted magnetic resonance technique: effect of lesion size and previous cone biopsy on tumor detectability.

OBJECTIVE: To evaluate the effects of previous cone biopsy and lesion size on detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion-weighted magnetic resonance imaging. METHODS: One hundred and thirteen patients with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W) and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed simultaneously were scored positive or negative for tumor and compared with histology at surgery. MRI tumor volumes, maximum radiological and histological dimensions were recorded. ROC analysis determined the MRI volume with optimal sensitivity/specificity for identifying tumor in those without and with prior cone biopsy/LLETZ and the maximum histological dimension for correctly identifying tumor with MRI. Mean apparent diffusion coefficients (ADCs) from tumor and adjacent normal epithelium were compared. RESULTS: Sensitivity and specificity for detecting tumor in those without (100%; 100% respectively) and with (80%; 78.9% respectively) prior cone biopsy/LLETZ were significantly different (p<0.001). Following cone biopsy/LLETZ, MRI tumor volume of 83 mm3 detected tumor with 80% sensitivity, 94.7% specificity; a 5.3mm maximal histological dimension was detected on MRI with 100% sensitivity, 100% specificity. Tumor ADCs were significantly lower (p<0.001) than paired normal epithelial tissue (median, 988×10(-6) mm2/s vs. 1564×10(-6) mm2/s) but neither tumor nor epithelial ADCs differed significantly between patients with or without prior cone biopsy/LLETZ (p=0.48 and 0.15, respectively). CONCLUSIONS: Endovaginal MRI with T2- and diffusion-weighted sequences has significantly lower sensitivity and specificity for tumor detection following cone biopsy/LLETZ.

Apparent diffusion coefficient as a predictive biomarker of prostate cancer progression: value of fast and slow diffusion components.

OBJECTIVE: The purpose of our study was to investigate whether fast and slow components of the apparent diffusion coefficient (ADC) from diffusion-weighted MR images could predict prostate cancer progression in patients managed by active surveillance. SUBJECTS AND METHODS: Eighty-one patients managed by active surveillance underwent diffusion-weighted MRI in addition to T2-weighted MRI using an endorectal technique. ADCs from tumor regions of interest were calculated using all b values (ADC(all)), b = 0-300 s/mm(2) (ADC(fast)), and b = 300-800 s/mm(2) (ADC(slow)). These parameters and tumor volumes were compared in those upgraded at subsequent biopsy (n = 14) versus those histologically stable (n = 41) and in evaluable patients who progressed to radical treatment (n = 16) versus those who did not (n = 64). Cox's regression was used to analyze the effect of parameter mean on time to treatment. RESULTS: ADC(all), ADC(fast), and ADC(slow) in patients upgraded on repeat biopsy were significantly lower than those who were stable (1,070 ± 110 vs 1,356 ± 357 × 10(-6)mm(2)/s, p < 0.001; 1,283 ± 188 vs 1,526 ± 397 × 10(-6)mm(2)/s, p = 0.004; 843 ± 74 vs 1,105 ± 285 × 10(-6) mm(2)/s, p < 0.001, respectively). Tumor volume was significantly higher in the upgraded group (0.86 ± 0.9 vs 0.26 ± 0.25 cm(3), p = 0.02). The lower ADC(slow) in patients who subsequently progressed to radical treatment approached significance (922 ± 256 vs 1,054 ± 235 × 10(-6) mm(2)/s, p = 0.053; hazard ratio, 0.991 for time to treatment). Tumor volume was significantly higher in the treated group (0.86 ± 0.85 cm(3) vs 0.32 ± 0.33 cm(3), p = 0.02). ADC(slow) and tumor volume were significant but independent predictors of upgrade on biopsy (p = 0.01 and 0.002, respectively). CONCLUSION: Both fast and slow diffusion components were significantly lower in tumors that were subsequently upgraded on histology. Both tumor volume and the true diffusion ADC(slow) were significant but independent predictors of histologic progression.