In vivo assessment of anisotropy of apparent magnetic susceptibility in white matter from a single orientation acquisition.

Multiple studies have reported a significant dependence of the effective transverse relaxation rate constant (R2*) and the phase of gradient-echo based (GRE) signal on the orientation of white matter fibres in the human brain. It has also been hypothesized that magnetic susceptibility, as obtained by single-orientation quantitative susceptibility mapping (QSM), exhibits such a dependence. In this study, we investigated this hypothesized relationship in a cohort of healthy volunteers. We show that R2* follows the predicted orientation dependence consistently across white matter regions, whereas the apparent magnetic susceptibility is related differently to fibre orientation across the brain and often in a complex non-monotonic manner. In addition, we explored the effect of fractional anisotropy measured by diffusion-weighted MRI on the strength of the orientation dependence and observed only a limited influence in many regions. However, with careful consideration of such an impact and the limitations imposed by the ill-posed nature of the dipole inversion process, it is possible to study magnetic susceptibility anisotropy in specific brain regions with a single orientation acquisition.

Prospective comparison of 18-FDG PET/CT and whole-body diffusion-weighted MRI in the assessment of multiple myeloma.

Magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG 18F-FDG PET-CT) are standard procedures for staging multiple myeloma (MM). Diffusion-weighted sequences applied to whole-body MRI (WB-DWI) improve its sensitivity. We compared the number of MM bone focal lesions (FLs) detected by 18F-FDG PET-CT and WB-DWI and evaluated the diagnostic performance of 18F-FDG PET-CT for diffuse infiltration. Thirty newly diagnosed MM patients prospectively underwent 18F-FDG PET-CT and WB-DWI. The criteria for skeletal region positivity were ≥ 1 focal bone lesions (FLs) and/or diffuse disease. MRI with the MY-RADS criteria was used as a reference standard for the diagnosis of diffuse infiltration. 18F-FDG PET-CT and WB-DWI were both interpreted as positive in 28/30 patients with an agreement of 1.00 (95% CI 0.77-1.00) between the two methods. The mean numbers of FLs were 16.7 detected by 18F-FDG PET-CT and 23.9 detected by WB-DWI (P = 0.028). WB-DWI detected more FLs in the skull (P = 0.001) and spine (P = 0.006). Agreement assessed using the prevalence and bias-corrected kappa index was moderate (0.40-0.60) for the spine, sternum-ribs and upper limbs and substantial (0.60-0.80) for the pelvis and lower limbs. As regards the diagnosis of diffuse bone marrow infiltration, the sensitivity, specificity and accuracy of 18F-FDG PET-CT were 0.75, 0.79 and 0.77, respectively. Although WB-DWI detected more FLs than did 18F-FDG PET-CT, there was no difference in the detection of bone disease on a per-patient basis. 18F-FDG PET-CT showed high performance, including for evaluation of diffuse infiltration.

Increased sensitivity and signal-to-noise ratio in diffusion-weighted MRI using multi-echo acquisitions.

Post-mortem diffusion MRI (dMRI) enables acquisitions of structural imaging data with otherwise unreachable resolutions - at the expense of longer scanning times. These data are typically acquired using highly segmented image acquisition strategies, thereby resulting in an incomplete signal decay before the MRI encoding continues. Especially in dMRI, with low signal intensities and lengthy contrast encoding, such temporal inefficiency translates into reduced image quality and longer scanning times. This study introduces Multi Echo (ME) acquisitions to dMRI on a human MRI system - a time-efficient approach, which increases SNR (Signal-to-Noise Ratio) and reduces noise bias for dMRI images. The benefit of the introduced ME-dMRI method was validated using numerical Monte Carlo simulations and showcased on a post-mortem brain of a wild chimpanzee. The proposed Maximum Likelihood Estimation echo combination results in an optimal SNR without detectable signal bias. The combined strategy comes at a small price in scanning time (here 30% additional) and leads to a substantial SNR increase (here white matter: ~ 1.6x, equivalent to 2.6 averages, grey matter: ~ 1.9x, equivalent to 3.6 averages) and a general reduction of the noise bias.

Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric high-grade glioma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric high-grade gliomas to various treatments. For areas in which scientific investigation was scarce, consensus was reached through an iterative process. RAPNO response assessment recommendations include the use of MRI of the brain and the spine, assessment of clinical status, and the use of corticosteroids or antiangiogenics. Imaging standards for brain and spine are defined. Compared with the recommendations for the management of adult high-grade glioma, for paediatrics there is inclusion of diffusion-weighted imaging and a higher reliance on T2-weighted fluid-attenuated inversion recovery. Consensus recommendations and response definitions have been established and, similar to other RAPNO recommendations, prospective validation in clinical trials is warranted.

Role of whole-body MRI for treatment response assessment in multiple myeloma: comparison between clinical response and imaging response.

BACKGROUND: Whole-body MRI (WB-MRI) including diffusion-weighted image (DWI) have been widely used in patients with multiple myeloma. However, evidence for the value of WB-MRI in the evaluation of treatment response remains sparse. Therefore, we evaluated the role of WB-MRI in the response assessment. METHODS: In our WB-MRI registry, we searched multiple myeloma patients treated with chemotherapy who underwent both baseline and follow-up WB-MRI scans. Clinical responses were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using IMWG criteria. Using RECIST 1.1, MD Anderson (MDA) criteria, and MDA-DWI criteria, imaging responses on WB-MRI were rated as CR, PR, SD, or PD by two radiologists independently. Then, discrepancy cases were resolved by consensus. Weighted Kappa analysis was performed to evaluate agreement between the imaging and clinical responses. The diagnostic accuracy of image responses in the evaluation of clinical CR, objective response (CR and PR), and PD was calculated. RESULTS: Forty-two eligible patients were included. There was moderate agreement between imaging and clinical responses (κ = 0.54 for RECIST 1.1, κ = 0.58 for MDA criteria, κ = 0.69 for MDA-DWI criteria). WB-MRI showed excellent diagnostic accuracy in assessment of clinical PD (sensitivity 88.9%, specificity 94.7%, positive predictive value [PPV] 84.2%, negative predictive value [NPV] 96.4% in all three imaging criteria). By contrast, WB-MRI showed low accuracy in assessment of clinical CR (sensitivity 4.5%, specificity 98.1%, PPV 50.0%, NPV 71.2% in all three imaging criteria). As to the clinical objective response, the diagnostic accuracy was higher in MDA-DWI criteria than RECIST 1.1 and MDA criteria (sensitivity/specificity/PPV/NPV, 84.2%/94.4%/98.0%/65.4, 54.4%/100%/100%/40.9, and 61.4%/94.4%/97.2%/43.6%, respectively). CONCLUSIONS: In the imaging response assessment of multiple myeloma, WB-MRI showed excellent performance in the evaluation of PD, but not in the assessment of CR or objective response. When adding DWI to imaging response criteria, diagnostic accuracy for objective response was improved and agreement between imaging and clinical responses was increased.

Non-invasive MR assessment of the microstructure and microcirculation in regional lymph nodes for rectal cancer: a study of intravoxel incoherent motion imaging.

BACKGROUND: The aim of this study is to evaluate the microstructure and microcirculation of regional lymph nodes (LNs) in rectal cancer by using non-invasive intravoxel incoherent motion MRI (IVIM-MRI), and to distinguish metastatic from non-metastatic LNs by quantitative parameters. METHODS: All recruited patients underwent IVIM-MRI (b = 0, 5, 10, 20, 30, 40, 60, 80, 100, 150, 200, 400, 600, 1000, 1500 and 2000 s/mm2) on a 3.0 T MRI system. One hundred sixty-eight regional LNs with a short-axis diameter equal to or greater than 5 mm from 116 patients were evaluated by two radiologists independently, including 78 malignant LNs and 90 benign LNs. The following parameters were assessed: the short-axis diameter (S), long-axis diameter (L), short- to long-axis diameter ratio (S/L), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion factor (f). Intraclass correlation coefficients (ICCs) were calculated to assess the interobserver agreement between two readers. Receiver operating characteristic curves were applied for analyzing statistically significant parameters. RESULTS: Interobserver agreement of IVIM-MRI parameters between two readers was excellent (ICCs> 0.75). The metastatic group exhibited higher S, L and D (P < 0.001), but lower f (P < 0.001) than the non-metastatic group. The area under the curve (95% CI, sensitivity, specificity) of the multi-parameter combined equation for D, f and S was 0.811 (0.744~0.868, 62.82%, 87.78%). The diagnostic performance of the multi-parameter model was better than that of an individual parameter (P < 0.05). CONCLUSION: IVIM-MRI parameters provided information about the microstructure and microcirculation of regional LNs in rectal cancer, also improved diagnostic performance in identifying metastatic LNs.

Visual assessment of diffusion weighted imaging infarct volume lacks accuracy and reliability.

PURPOSE: The DAWN trial (Diffusion weighted imaging or CT perfusion Assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing Neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria. MATERIALS AND METHODS: 18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 MR scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters' visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics. RESULTS: The mean accuracy of raters was <90% for all volume cut-points. Inter-rater agreement was below substantial for each DWI infarct volume cut-off points. Intra-rater agreement was substantial for 55-83% of raters, depending on the selected cut-off points. Applying DAWN criteria with visual estimates instead of RAPID measurements led to 19% erroneous thrombectomy decisions, and showed a lack of reproducibility. CONCLUSION: The visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria.

Low frequency oscillating gradient spin-echo sequences improve sensitivity to axon diameter: An experimental study in viable nerve tissue.

Mapping axon diameters within the central and peripheral nervous system could play an important role in our understanding of nerve pathways, and help diagnose and monitor an array of neurological disorders. Numerous diffusion MRI methods have been proposed for imaging axon diameters, most of which use conventional single diffusion encoding (SDE) spin echo sequences. However, a growing number of studies show that oscillating gradient spin echo (OGSE) sequences can provide additional advantages over conventional SDE sequences. Recent theoretical results suggest that this is especially the case in realistic scenarios, such as when fibres have unknown or dispersed orientation. In the present study, we adopt the ActiveAx approach to experimentally investigate the extent of these advantages by comparing the performances of SDE and trapezoidal OGSE in viable nerve tissue. We optimise SDE and OGSE ActiveAx protocols for a rat peripheral nerve tissue and test their performance using Monte Carlo simulations and a 800 mT/m gradient strength pre-clinical imaging experiment. The imaging experiment uses excised sciatic nerve from a rat's leg placed in a MRI compatible viable isolated tissue (VIT) maintenance chamber, which keeps the tissue in a viable physiological state that preserves the structural complexity of the nerve and enables lengthy scan times. We compare model estimates to histology, which we perform on the nerve post scanning. Optimisation produces a three-shell SDE and OGSE ActiveAx protocol, with the OGSE protocol consisting of one SDE sequence and two low-frequency oscillating gradient waveform sequences. Both simulation and imaging results show that the OGSE ActiveAx estimates of the axon diameter index have a higher accuracy and a higher precision compared to those from SDE. Histology estimates of the axon diameter index in our nerve tissue samples are 4-5.8 µm and these are excellently matched with the OGSE estimates 4.2-6.5 µm, while SDE overestimates at 5.2-8 µm for the same sample. We found OGSE estimates to be more precise with on average a 0.5 µm standard deviation compared to the SDE estimates which have a 2 µm standard deviation. When testing the robustness of the estimates when the number of the diffusion gradient directions reduces, we found that both OGSE and SDE estimates are affected, however OGSE is more robust to these changes than the SDE. Overall, these results suggest, quantitatively and in in vivo conditions, that low-frequency OGSE sequences may provide improved accuracy of axon diameter mapping compared to standard SDE sequences.

Technical Note: A safe, cheap, and easy-to-use isotropic diffusion MRI phantom for clinical and multicenter studies.

PURPOSE: Since Diffusion Weighted Imaging (DWI) data acquisition and processing are not standardized, substantial differences in DWI derived measures such as Apparent Diffusion Coefficient (ADC) may arise which are related to the acquisition or MRI processing method, but not to the sample under study. Quality assurance using a standardized test object, or phantom, is a key factor in standardizing DWI across scanners. METHODS: Current diffusion phantoms are either complex to use, not available in larger quantities, contain substances unwanted in a clinical environment, or are expensive. A diffusion phantom based on a polyvinylpyrrolidone (PVP) solution, together with a phantom holder, is presented and compared to existing diffusion phantoms for use in clinical DWI scans. An ADC vs. temperature calibration curve was obtained. RESULTS: ADC of the phantom (808 to 857 ± 0.2 mm2 /s) is in the same range as ADC values found in brain tissue. ADC measurements are highly reproducible across time with an intra-class correlation coefficient of > 0.8. ADC as function of temperature (in Kelvin) can be estimated as ADCm(T)=[exp(-7.09)·exp-2903.81T-1293.55] with a total uncertainty (95% confidence limit) of ± 1.7%. CONCLUSION: We present an isotropic diffusion MRI phantom, together with its temperature calibration curve, that is easy-to-use in a clinical environment, cost-effective, reproducible to produce, and that contains no harmful substances.

Image quality assessment of single-shot turbo spin echo diffusion-weighted imaging with parallel imaging technique: a phantom study.

OBJECTIVE: This study aimed to evaluate the image quality and apparent diffusion coefficient (ADC) values of single-shot turbo spin echo (TSE) diffusion-weighted (DW) images obtained using a parallel imaging (PI) technique. METHODS: All measurements were performed on a 3.0-T whole-body MRI system and 32-channel phased-array coil. Signal-to-noise ratio (SNR) and ADC values were measured with a DW imaging (DWI) phantom comprising granulated sugar and agar. The SNRs were calculated using a subtraction method and compared among TSE-DW images at acceleration factors (AFs) of 1-4. Image blur was visually assessed on TSE-DW images of a pin phantom at AFs of 1-4. The ADC values were calculated using DW images with b = 0 and 1000 s mm(-2). The ADC values of TSE-DW images and echo-planar imaging EPI-DW images were compared. RESULTS: The SNRs decreased as AFs increased, despite selecting the shortest echo time. A lower AF caused increased image blur in the phase-encoding direction. The ADC values of TSE-DWI tended to be lower than those of EPI-DWI, and AFs of 3 and 4 yielded variable ADC values on TSE-DW images. CONCLUSION: TSE-DWI with an AF of 3 or 4 yielded reduced SNRs; in addition, the image noise and artefacts associated with PI technique may have affected ADC measurements, despite improving image blur in the phase-encoding direction. ADVANCES IN KNOWLEDGE: Optimizing the imaging parameters of TSE-DWI is useful for providing good image quality and accurate ADC measurements.

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. METHODS: The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. RESULTS: Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. CONCLUSIONS: Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke.

Assessment of apparent diffusion coefficient of normal fetal brain development from gestational age week 24 up to term age: a preliminary study.

OBJECTIVES: This study was designed to investigate the feasibility of apparent diffusion coefficient (ADC) values in evaluating normal fetal brain development from gestational week 24 up to term age. METHODS: Diffusion-weighted imaging (DWI) was performed on 40 normal fetuses (with normal results on sonography and normal fetal MRI results), with two b-values of 0 and 600 s/mm² in the three (x, y, z) orthogonal axes. Ten regions of interest (ROIs) were manually placed symmetrically in the bilateral frontal white matter (FWM), occipital white matter (OWM), thalamus (THAL), basal ganglia (BG), and cerebellar hemispheres (CH). ADC values of the ten ROIs in all subjects were measured by two radiologists independently. One-way ANOVA was used to calculate the differences among the five regions in the fetal brain and linear regression analysis was used to evaluate the correlation between ADC values and gestational age (GA). p < 0.05 was considered significantly different. RESULTS: Mean GA was 31.3 ± 3.9 (range 24-41) weeks. The overall mean ADC values (× 10⁻6 mm²/s) of the fetuses were 1,800 ± 214 (FWM), 1,400 ± 100 (BG), 1,300 ± 126 (THAL), 1,700 ± 133 (OWM) and 1,400 ± 155 (CH), respectively. The ADC value of BG was not significantly different from those of THAL and CH, while the other four ROIs had significant differences with each other. The ADC values of BG, THAL, OWM and CH had strong negative correlations with increasing GA (R were -0.568, -0.716, -0.830 and -0.700, respectively, all p < 0.01), OWM declined fastest with GA, followed by CH and THAL, the slowest being BG. The ADC value of FWM had no significant change with GA (p = 0.366). CONCLUSIONS: The measurement of ADC values is feasible to evaluate fetal brain development with high reliability and reproducibility.

The reliability of fetal MRI in the assessment of brain malformations.

OBJECTIVES: To assess the inter- and intraobserver reliability of different fetal MRI measurements in cases of fetal brain malformations and to examine the concordance between ultrasonography (US) and MRI findings. METHODS: Fetal brain MRIs and US findings of 56 pregnant women were retrieved from the institutional database. Standardized fetal brain MRI measurements were performed by 4 observers, and the inter- and intraobserver reliability was determined. Additionally, US and MRI findings were retrospectively compared. RESULTS: The interobserver intraclass correlation coefficient (ICC) was above 0.9 for the cerebellum and posterior horn of the lateral ventricle. The measurements regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus callosum (0.63) showed poor reliability. Overall, the intraobserver reliability was greater than the interobserver reliability. US and MRI findings were discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a change of diagnosis in 3.6%, and excluding pathological findings suspected on US in 7.1%. CONCLUSIONS: Fetal MRI is a valuable complement to US in the investigation of fetal brain malformations. The reliability of most parameters was high, except for the measurements of the third and fourth ventricles and the corpus callosum.

Clinical assessment of standard and generalized autocalibrating partially parallel acquisition diffusion imaging: effects of reduction factor and spatial resolution.

BACKGROUND AND PURPOSE: PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique. MATERIALS AND METHODS: Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence. RESULTS: Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions. CONCLUSIONS: PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

Diffusion-weighted imaging in the assessment of brain abscesses therapy.

BACKGROUND AND PURPOSE: Surgically or conservatively treated brain abscesses may resolve, or pus may re-accumulate, requiring further intervention or treatment change. We hypothesized that diffusion-weighted (DW) imaging is useful in depicting features of abscesses related to therapeutic success or failure. METHODS: Conventional contrast-enhanced T1- and T2-weighted imaging and DW imaging were performed in seven patients (aged 30-69 years) with proved pyogenic brain abscesses. The center of the abscess was qualitatively and quantitatively analyzed at initial and follow-up imaging in all patients. We correlated the signal intensity on trace DW images and the apparent diffusion coefficients (ADCs) with the clinical and laboratory data, particularly with respect to treatment failure and repeat therapy. RESULTS: Surgical drainage was performed in six patients; one patient was treated with only antibiotics. All abscess cavities initially had high signal intensity (restricted diffusion) on DW images, with a mean ADC value of 0.52 x 10 (-3)mm (2)/s. Low signal intensity at DW imaging with high ADC were seen on follow-up images in the patient receiving medication and in four patients in whom the abscesses were drained; this correlated with a good therapeutic response. Two patients underwent drainage; their second follow-up DW images showed areas of high signal intensity and low ADC values suggesting re-accumulation of pus. Increased C-reactive protein level and WBC count correlated well with DW image findings. CONCLUSION: DW imaging was superior to conventional MR imaging in evaluating the success or failure of abscess therapy. Restricted diffusion in a drained abscess corresponded to pus.