Introduction of a new simple dynamic phantom for physical BOLD effect simulation.

OBJECTIVE: To propose a new method of simulating the BOLD contrast using a dynamic, easy to construct and operate, low-cost physical phantom. MATERIALS AND METHODS: A structure of thin pipelines passing through a gel volume was used to simulate blood vessels in human tissue. Quantitative T2*, R2* measurements were used to study the signal change of the phantom. BOLD fMRI experiments and analysis were performed to evaluate its potential use as an fMRI simulator. RESULTS: Experimental T2*, R2* measurements showed similar behavior with published references. BOLD contrast was successfully achieved with the proposed method. In addition, there were several proposed parameters, like the angle of the phantom relative to B0, which can easily adjust the signal change and the activation area. Coefficients of variation showed good reproducibility within a month period. Statistical t maps were produced with in-house software for the BOLD measurements. DISCUSSION: T2*maps and BOLD images confirm the potential use of this phantom as an fMRI simulator and also as a tool for studying sensitivity and specificity of BOLD sequences/algorithms.

End to end comparison of surface-guided imaging versus stereoscopic X-rays for the SRS treatment of multiple metastases with a single isocenter using 3D anthropomorphic gel phantoms.

INTRODUCTION: Two end-to-end tests evaluate the accuracy of a surface-guided radiation therapy (SGRT) system (CRAD Catalyst HD) for position verification in comparison to a stereoscopic x-ray imaging system (Brainlab Exactrac ) for single-isocenter, multiple metastases stereotactic radiosurgery (SRS) using 3D polymer gel inserts. MATERIALS AND METHODS: A 3D-printed phantom (Prime phantom, RTsafe PC, Athens, Greece) with two separate cylindrical polymer gel inserts were immobilized in open-face masks and treated with a single isocentric, multitarget SRS plan. Planning was done in Brainlab (Elements) to treat five metastatic lesions in one fraction, and initial setup was done using cone beam computed tomography. Positional verification was done using orthogonal X-ray imaging (Brainlab Exactrac) and/or a surface imaging system (CRAD Catalyst HD, Uppsala, Sweden), and shift discrepancies were recorded for each couch angle. Forty-two hours after irradiation, the gel phantom was scanned in a 1.5 Tesla MRI, and images were fused with the patient computed tomography data/structure set for further analysis of spatial dose distribution. RESULTS: Discrepancies between the CRAD Catalyst HD system and Brainlab Exactrac were <1 mm in the translational direction and <0.5° in the angular direction at noncoplanar couch angles. Dose parameters (DMean% , D95% ) and 3D gamma index passing rates were evaluated for both setup modalities for each planned target volume (PTV) at a variety of thresholds: 3%/2 mm (Exactrac≥93.1% and CRAD ≥87.2%), 5%/2 mm (Exactrac≥95.6% and CRAD ≥94.6%), and 5%/1 mm (Exactrac≥81.8% and CRAD ≥83.7%). CONCLUSION: Dose metrics for a setup with surface imaging was found to be consistent with setup using x-ray imaging, demonstrating high accuracy and reproducibility for treatment delivery. Results indicate the feasibility of using surface imaging for position verification at noncoplanar couch angles for single-isocenter, multiple-target SRS using end-to-end quality assurance (QA) testing with 3D polymer gel dosimetry.

Brain stereotactic radiosurgery using MR-guided online adaptive planning for daily setup variation: An end-to-end test.

Online magnetic resonance (MR)-guided radiotherapy is expected to benefit brain stereotactic radiosurgery (SRS) due to superior soft tissue contrast and capability of daily adaptive planning. The purpose of this study was to investigate daily adaptive plan quality with setup variations and to perform an end-to-end test for brain SRS with multiple metastases treated with a 1.5-Tesla MR-Linac (MRL). The RTsafe PseudoPatient Prime brain phantom was used with a delineation insert that includes two predefined structures mimicking gadolinium contrast-enhanced brain lesions. Daily adaptive plans were generated using six preset and six random setup variations. Two adaptive plans per daily MR image were generated using the adapt-to-position (ATP) and adapt-to-shape (ATS) workflows. An adaptive patient plan was generated on a diagnostic MR image with simulated translational and rotational daily setup variation and was compared with the reference plan. All adaptive plans were compared with the reference plan using the target coverage, Paddick conformity index, gradient index (GI), Brain V12 or V20, optimization time and total monitor units. Target doses were measured as an end-to-end test with two ionization chambers inserted into the phantom. With preset translational variations, V12 from the ATS plan was 17% lower than that of the ATP plan. With a larger daily setup variation, GI and V12 of the ATS plan were 10% and 16% lower than those of the ATP plan, respectively. Compared to the ATP plans, the plan quality index of the ATS plans was more consistent with the reference plan, and within 5% in both phantom and patient plans. The differences between the measured and planned target doses were within 1% for both treatment workflows. Treating brain SRS using an MRL is feasible and could achieve satisfactory dosimetric goals. Setup uncertainties could be accounted for using online plan adaptation. The ATS workflow achieved better dosimetric results than the ATP workflow at the cost of longer optimization time.

T2 Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance.

BACKGROUND: Although diffusely abnormal white matter (DAWM) is commonly seen in multiple sclerosis (MS), it is rarely considered in clinical/imaging studies. PURPOSE: To evaluate quantitative markers of microstructural changes in DAWM of patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) in relation to MS lesions and degree of neurocognitive impairment, by using a multi-echo spin echo (MESE) Proton Density PD-to-T2 sequence. STUDY TYPE: Prospective, cross-sectional. POPULATION: Thirty-seven RR-MS patients, 33 CIS patients, and 52 healthy controls. FIELD STRENGTH/SEQUENCE: 1.5 T/T1-, T2-weighted, fluid-attenuated inversion recovery, and MESE sequences. ASSESSMENT: Long T2, short T2, and myelin water fraction (MWF) values were estimated as indices of intra/extracellular water content and myelin content, respectively, in DAWM, posterior periventricular normal appearing white matter (NAWM), and focal MS lesions, classified according to their signal intensity on T1 sequences. Patients were, also, administered a battery of neuropsychological tests. STATISTICAL TESTS: Comparisons of T2 and MWF values in DAWM, NAWM, and MS lesions were examined, using two-way mixed analyses of variance. Associations of Grooved Pegboard performance with T2 and MWF values in DAWM and NAWM were assessed using Pearson correlation coefficients. RESULTS: T2 and MWF values of DAWM were intermediate between the respective values of NAWM and T1 hypointense focal lesions, while there was no difference between the respective values of DAWM and T1-isointense lesions. T2 values in DAWM were strongly associated with visuomotor performance in CIS patients. DATA CONCLUSION: Intra/extracellular water and myelin water content of DAWM are similar to those of T1-isointense lesions and predict visuomotor performance in CIS patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Validation of PTV margin for Gamma Knife Icon frameless treatment using a PseudoPatient® Prime anthropomorphic phantom.

The Gamma Knife Icon allows the treatment of brain tumors mask-based single-fraction or fractionated treatment schemes. In clinic, uniform axial expansion of 1 mm around the gross tumor volume (GTV) and a 1.5 mm expansion in the superior and inferior directions are used to generate the planning target volume (PTV). The purpose of the study was to validate this margin scheme with two clinical scenarios: (a) the patient's head remaining right below the high-definition motion management (HDMM) threshold, and (b) frequent treatment interruptions followed by plan adaptation induced by large pitch head motion. A remote-controlled head assembly was used to control the motion of a PseudoPatient® Prime head phantom; for dosimetric evaluations, an ionization chamber, EBT3 films, and polymer gels were used. These measurements were compared with those from the Gamma Knife plan. For the absolute dose measurements using an ionization chamber, the percentage differences for both targets were less than 3.0% for all scenarios, which was within the expected tolerance. For the film measurements, the two-dimensional (2D) gamma index with a 2%/2 mm criterion showed the passing rates of ≥87% in all scenarios except the scenario 1. The results of Gel measurements showed that GTV (D100 ) was covered by the prescription dose and PTV (D95 ) was well above the planned dose by up to 5.6% and the largest geometric PTV offset was 0.8 mm for all scenarios. In conclusion, the current margin scheme with HDMM setting is adequate for a typical patient's intrafractional motion.

Age-related deep white matter changes in myelin and water content: A T2 relaxometry study.

BACKGROUND: According to the retrogenesis hypothesis, the rate of age-related changes in white matter (WM) myelin content varies between early myelinating (parietal, occipital) and late myelinating (prefrontal, lateral-posterior temporal) areas. The multiecho spin echo (MESE), PD-to-T2 -weighted sequence provides an index of myelin content (myelin water fraction [MWF]) derived from measurements of myelin water (via the short T2 component [10-50 msec]) and intra- and extracellular water (via the long T2 component [>50-200 msec]). PURPOSE: To assess the shape and regional variations in the rate of age-related myelin and water content changes in deep WM regions using the MESE sequence. STUDY TYPE: Prospective, cross-sectional. POPULATION: In all, 90 healthy adults aged 22-81 years. FIELD STRENGTH/SEQUENCE: 1.5T/ T1 w, T2 w, fluid attenuated inversion recovery (FLAIR), MESE sequences. ASSESSMENT: Short T2 , long T2 , and MWF values were measured in prefrontal, parietal, lateral-posterior temporal, and occipital normal-appearing WM (NAWM) areas. STATISTICAL TESTS: Linear and quadratic effects of age on long T2 and MWF were assessed through regression analyses. Regional variations in the effect of age on long T2 and MWF values at both the individual and group level were examined, using regression and analysis of covariance (ANCOVA) analyses, respectively, controlling for total WM volume. RESULTS: The rate of age-related changes in long T2 and MWF was higher for older persons and a significant increase or decline, respectively, was first noted at 60-69 years (P < 0.0033). MWF values peaked earlier (at 30 years of age) and displayed a steeper age-related reduction in prefrontal and lateral-posterior temporal NAWM as compared with the occipital lobes (P < 0.05). The opposite pattern of age-related effect was found for long T2 values. DATA CONCLUSION: Significant age-related reductions in myelin content were closely followed by corresponding increases in intra- and extracellular water content. These changes were more pronounced among elderly people and followed an anterior-posterior pattern. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1393-1404.

Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment.

BACKGROUND: Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T2 relaxation time technique may serve as a more direct measure of myelin content. PURPOSE/HYPOTHESIS: The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment. POPULATION: The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33). FIELD STRENGTH/SEQUENCE ASSESSMENT: Long T2 , short T2 , and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants. STATISTICAL TESTS, RESULTS: AD patients displayed higher age-adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T2 /MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T2 and MWF values in these regions. DATA CONCLUSION: Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1359-1372.

Evaluation of foot hypoperfusion and estimation of percutaneous transluminal angioplasty outcome in patients with critical limb ischemia using intravoxel incoherent motion microperfusion MRI.

OBJECTIVES: To emerge hypoperfusion of lower limbs in patients with critical limb ischemia (CLI) using Intravoxel Incoherent Motion microperfusion magnetic resonance imaging (IVIM-MRI). Moreover to examine the ability of IVIM-MRI to differentiate patients with severe peripheral arterial disease (PAD) from normal subjects and evaluate the percutaneous transluminal angioplasty (PTA) results in patients with CLI. METHODS: Eight patients who presented with CLI and six healthy volunteers were examined. The patients underwent IVIM-MRI of lower extremity before and following PTA. The imaging protocol included sagittal diffusion-weighted (DW) sequences. DW images were analyzed and color parametric maps of the micro-circulation of blood inside the capillary network (D*) were constructed. The studies were evaluated by two observers to define interobserver reproducibility. RESULTS: Technical success was achieved in all patients (8/8). The mean ankle-brachial index increased from 0.35 ± 0.2 to 0.76 ± 0.25 (p < 0.05). Successful revascularization improved IVIM microperfusion. Mean D* increased from 279.88 ± 13.47 10-5 mm2/s to 331.51 ± 31 10-5 mm2/s, following PTA, p < 0.05. Moreover, PAD patients presented lower D* values as compared to healthy individuals (279.88 ± 13.47 10-5 mm2/s vs 332.47 ± 22.95 10-5 mm2/s, p < 0.05, respectively). Good interobserver agreement was obtained with an ICC = 0.84 (95% CI 0.64-0.93). CONCLUSIONS: IVIM-MRI can detect differences in microperfusion between patients with PAD and healthy individuals. Moreover, significant restitution of IVIM microperfusion is found following successful PTA. ADVANCES IN KNOWLEDGE: IVIM-MRI is a safe, reproducible and effective modality for evaluation of lower limb hypoperfusion in patients with PAD. It seems also to be a helpful tool to detect changes of tissue perfusion in patients with CLI following revascularization.

Myelin content changes in Clinically Isolated Syndrome and Relapsing- Remitting Multiple Sclerosis: Associations with lesion type and severity of visuomotor impairment.

BACKGROUND: Cognitive disturbances occur in patients with Relapsing Remitting Multiple Sclerosis (RR-MS) and Clinically Isolated Syndrome (CIS). The Multi-Echo-Spin-Echo (MESE) T2-weighted sequence quantifies demyelination, the pathological hallmark of MS, but has not been used for the documentation of the potential relationship between anatomically specific demyelinating changes and cognitive impairment in MS. PURPOSE: To identify markers of regional demyelination in patients with RR-MS and CIS in relation to clinical variables and severity of cognitive impairment. METHODS AND MATERIALS: 37 RR-MS patients, 39 CIS patients and 52 healthy controls (HC) were examined using the MESE sequence. Long T2 and myelin water fraction (MWF) values were measured, serving as indices of intra/extracellular water content and myelin content, respectively, in focal white matter lesions and 12 normal appearing white matter (NAWM) areas of the patients and HC. A comprehensive neuropsychological assessment was administered to all patients. RESULTS: RR-MS patients showed widespread long T2 increases and MWF reductions in NAWM, compared to the respective values of HC (p < 0.001), which correlated with total lesion volume. Among RR-MS patients illness duration correlated negatively with MWF in right hemisphere frontal and periventricular NAWM areas (and positively with corresponding long T2 values). MWF values were lower in the CIS, as compared to the HC group, in the temporal, frontal and periventricular NAWM areas. Focal demyelinating lesions displayed variable higher T2 and lower MWF values, compared to NAWM, closely corresponding to their intensity on T1 sequences. Reduced MWF values and increased long T2 values in right periventricular NAWM were significantly associated with poor visuomotor performance. CONCLUSION: The MESE sequence affords accurate estimation of myelin and water content in NAWM and focal lesions in RR-MS and CIS patients, by means of the MWF and long T2 values, respectively, providing a sensitive index of demyelination associated with visuomotor deficits.

The Significance of Echo Time in fMRI BOLD Contrast: A Clinical Study during Motor and Visual Activation Tasks at 1.5 T.

Blood Oxygen Level Dependent (BOLD) is a commonly-used MR imaging technique in studying brain function. The BOLD signal can be strongly affected by specific sequence parameters, especially in small field strengths. Previous small-scale studies have investigated the effect of TE on BOLD contrast. This study evaluates the dependence of fMRI results on echo time (TE) during concurrent activation of the visual and motor cortex at 1.5 T in a larger sample of 21 healthy volunteers. The experiment was repeated using two different TE values (50 and 70 ms) in counterbalanced order. Furthermore, T2* measurements of the gray matter were performed. Results indicated that both peak beta value and number of voxels were significantly higher using TE = 70 than TE = 50 ms in primary motor, primary somatosensory and supplementary motor cortices (p < 0.007). In addition, the amplitude of activation in visual cortices and the dorsal premotor area was also higher using TE = 70 ms (p < 0.001). Gray matter T2* of the corresponding areas did not vary significantly. In conclusion, the optimal TE value (among the two studied) for visual and motor activity is 70 ms affecting both the amplitude and extent of regional hemodynamic activation.

Inverse Laplace transform and multiexponential fitting analysis of T2 relaxometry data: a phantom study with aqueous and fat containing samples.

BACKGROUND: The inverse Laplace transform (ILT) is the most widely used method for T2 relaxometry data analysis. This study examines the qualitative agreement of ILT and a proposed multiexponential (Mexp method) regarding the number of T2 components. We performed a feasibility study for the voxelwise characterisation of heterogeneous tissue with T2 relaxometry. METHODS: Eleven samples of aqueous, fatty and mixed composition were analysed using ILT and Mexp. The phantom was imaged using a 1.5-T system with a single slice T2 relaxometry 25-echo Carr-Purcell-Meiboom-Gill sequence in order to obtain the T2 decay curve with 25 equidistant echo times. The adjusted R2 goodness of fit criterion was used to determine the number of T2 components using the Mexp method on a voxel-based analysis. Comparison of mean and standard deviation of T2 values for both methods was performed by fitting a Gaussian function to the ILT resulting vector. RESULTS: Phantom results showed pure monoexponential decay for acetone and water and pure biexponential behaviour for corn oil, egg yolk, and 35% fat milk cream, while mixtures of egg whites and yolks as well as milk creams with 12-20% fatty composition exhibit mixed monoexponential and biexponential behaviour at different fractions. The number of T2 components by the Mexp method was compared to the ILT-derived spectrum as ground truth. CONCLUSIONS: Mexp analysis with the adjusted R2 criterion can be used for the detection of the T2 distribution of aqueous, fatty and mixed samples with the added advantage of voxelwise mapping.

Apparent diffusion coefficient measurements on a novel diffusion weighted MRI phantom utilizing EPI and HASTE sequences.

PURPOSE: The aim of this study is to introduce a novel DWI-MRI phantom and to compare Apparent Diffusion Coefficient (ADC) measurements, utilizing EPI-DWI and HASTE-DWI sequences and two different fitting algorithms. MATERIALS AND METHODS: 23 test tubes with different sucrose concentrations and polyacrylamide gels were used as a phantom for ADC measurements. The phantom was scanned on a clinical MRI system (1.5 T) over a two-month period utilizing an EPI-DWI and a HASTE-DWI sequence. ADC maps were calculated using a Weighted Linear (WL) and a Non Linear (NL) fitting algorithm. Measurements were performed with two sequences and two fitting algorithms. Geometric Distortions (GD), Ghosting Ratios (GR) and Signal to Structured Noise Ratios (SSNRs) were estimated using both sequences from the resultant ADC parametric maps. RESULTS: Polyacrylamide gels reveal lower coefficient of variation (CV%) as compared to sucrose solutions. ADC measurements performed with WL and NL algorithms reveal identical results with both sequences. WL and NL algorithms require approx. 3 s and 7 min respectively, for a single slice. EPI-DWI reveals a mean percent ADC value difference of (+4.5%) as compared to HASTE-DWI, regardless the type of fitting algorithm. CONCLUSION: Polyacrylamide gels can serve as a better means for simulating ADC values, compared with sucrose solutions used in this study. WL can be proposed as the method for ADC measurements in daily clinical practice. WL is significantly faster than NL fitting method and equally precise. SSNR measured directly on ADC maps is an excellent means for testing the precision of ADC measurements.