The development and optimisation of 3D black-blood R2* mapping of the carotid artery wall

PurposeTo develop and optimise a 3D black-blood R₂* mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering.MethodsTwo different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R₂*, and the sternocleidomastoid muscle R₂* were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression.ResultsAll sequences resulted in comparable R₂* measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression.ConclusionThe use of blood-suppression preparation methods does not affect the measurement of R₂*. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R₂* measurements of the carotid vessel wall.     

Comparison between multi-echo T2* with and without fat saturation pulse for quantification of liver iron overload

Purpose

To test a magnetic resonance image (MRI) technique that uses an additional pulse in multi-echo T2* sequence that works to suppress the fat signal, in subjects with liver iron overload and concomitant presence of fat in the liver, which have been revealed as a major drawback that compromises the correct iron quantification by MRI.

Materials and Methods

Fifty magnetic resonance images of the liver (1.5 T scanner) of individuals with blood ferritin increases were retrospectively reviewed for the presence of steatosis, using the sequence in and out of phase, and iron overloading, using two sequences T2 * multi-echo: one standard and other with additional fat suppression pulse. T2 * values and their standard deviations were analyzed statistically.

Results

Our results showed that a significantly lower standard deviation of T2* values is obtained when the fat saturation pulse is applied in patients with steatosis. We found that modulation of fat signal on liver iron overload resulted in a different categorization of some patients. In one case, the patient was re-classified within normal levels of liver iron.

Conclusion

Our findings may contribute to a better measure of liver iron overload with relevant implications for patient treatment and care.     

A purpose-built neck coil for black-blood DANTE-prepared carotid artery imaging at 7 T

Atherosclerotic plaques in the bifurcation of the carotid arteries can pose a significant health risk due to possible plaque rupture and subsequent stroke. The assessment of plaques, and evaluation of the risk they pose, can be performed with Black-Blood (BB) vessel wall magnetic resonance imaging. However, resolution at standard clinical field strengths (up to 3 T) is limited, hampering reliable assessment and diagnosis. The aim of this study was to investigate the benefits of 7 T MRI using a BB application that has been successful at clinical field strengths. Therefore, for BB imaging, each sequence was preceded with ‘Delay Alternating with Nutation for Tailored Excitation’ (DANTE) preparation pulses for blood signal suppression. A coil comprising a 4-channel Tx array was designed and built to provide the required excitation coverage for the DANTE train; and a 4-channel Rx array was constructed to target the carotid bifurcation. Human and phantom results showed satisfactory blood suppression and comparable SNR and CNR to 3 T, therefore demonstrating the feasibility of the application at 7 T. However, the imposed SAR restrictions led to long scan times and subsequent motion artifacts. Thus, more accurate local SAR supervision schemes are required which could lead to a further improvement of BB DANTE vessel wall imaging at 7 T.     

Quantitative MRI: Defining repeatability,reproducibility and accuracy for prostate cancer imaging biomarker development

IntroductionQuantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response.Materials and methodsADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms.ResultsOverall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between −8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners.ConclusionRepeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.     

Quantitative susceptibility mapping using principles of echo shifting with a train of observations sequence on 1.5 T MRI

PurposeTo evaluate the accuracy of susceptibility estimated from the principles of echo shifting with a train of observations (PRESTO) sequence using a 1.5 T MRI system, we conducted experiments on the human brain using the PRESTO sequence and compared our results with the susceptibility obtained from spoiled gradient-recalled echo (GRE) sequence with flow compensation using quantitative susceptibility mapping (QSM) reconstruction.Materials and methodsExperiments on the human brain were conducted on 12 healthy volunteers (27 ± 4 years) using PRESTO and spoiled GRE sequences on a 1.5 T scanner. The PRESTO sequence is an echo-shifted gradient echo sequence that allows high susceptibility sensitivity and rapid acquisition because of TE > TR compared with the spoiled GRE sequence. QSM analysis was performed on the obtained phase images using the iLSQR method. Estimated susceptibility maps were used for region of interest analyses and estimation of line profiles through iron-rich tissue and major vessels.ResultsOur results demonstrated that susceptibility maps were accurately estimated, without error, by QSM analysis of PRESTO and spoiled GRE sequences. Acquisition time in the PRESTO sequence was reduced by 43% compared with that in the spoiled GRE sequence. Differences did exist between susceptibility maps in PRESTO and spoiled GRE sequences for visualization and quantitative values of major blood vessels and the areas around themConclusionThe PRESTO sequence enables correct estimation of tissue susceptibility with rapid acquisition and may be useful for QSM analysis of clinical use of 1.5 T scanners.     

High resolution simultaneous imaging of intracranial and extracranial arterial wall with improved cerebrospinal fluid suppression

PurposeTo develop a technique for three dimensional (3D) high resolution joint imaging of intracranial and extracranial arterial walls with improved cerebrospinal fluid (CSF) suppression and good blood suppression based on T1 weighted sampling perfection with application optimized contrast using different angle evolutions (T1w-SPACE) and to compare this technique (hereafter, iSPACE) with alternating with nutation for tailored excitation (DANTE) prepared SPACE sequence (DANTE-SPACE) for their CSF suppression performance around the mid cerebral arteries (MCA) and blood suppression at carotid arteries.Materials and methodsEight volunteers and twelve patients were prospectively recruited in this institutional review board approved study. A custom designed 32-channel coil set covering the intracranial and extracranial arteries was used for signal reception. Imaging was performed in each subject using DANTE-SPACE and iSPACE. Signal-to-noise ratios (SNR) of the vessel walls at the MCA and carotid arteries, and contrast-to-noise ratios (CNR) between vessel wall and CSF at the MCA and between vessel wall and lumen at carotid arteries from the two sequences were compared.ResultsIn volunteers, contrast between CSF and white matter (surrogate for vessel wall signal) at the M2 segments in iSPACE was 67.9% higher than in DANTE-SPACE. At the carotid region, the SNR of vessel wall in iSPACE was 11.6% higher than DANTE-SPACE while the CNR in iSPACE was 13% higher than DANTE-SPACE. In patients, images with 0.6 mm isotropic resolution were obtained in 7.5 min. iSPACE showed 70.9% improvement in CNR between plaque and CSF at the M2 segments compared to DANTE-SPACE.ConclusionSimultaneous extracranial and intracranial arterial wall imaging using iSPACE improved CSF suppression significantly at the M2 segment of MCA while blood suppression was comparable to DANTE-SPACE. The technique achieved 3D images with 0.6 mm isotropic spatial resolution and took 7.5 min using a custom made coil set. Using this technique, intracranial plaque visualization was improved with no observable image SNR degradation.     

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets

PurposeDeep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes.MethodsFive patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences.ResultsThe mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead.ConclusionThe imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location.     

变延迟进动定制激发(DANTE)序列在工程中的优化设计

变延迟进动定制激发（Delays Alternating with Nutation for Tailored Excitation,DANTE）序列作为一种黑血预脉冲序列,通过连续施加小角度激发脉冲,以及结合散相梯度,使得流动物质和静态物质达到不同的稳态,从而抑制流动的血液.对于静态物质而言,施加DANTE序列后在图像等间隔的位置会出现暗条纹,暗条纹的宽度与梯度幅值和小单元持续时间乘积相关：乘积越大,暗纹宽度越小.对于动态物质而言,为达到较好的抑制效果,需要增加整个DANTE序列模块的准备时间,并且增大梯度幅值和小单元持续时间的乘积.因此,该方法对于梯度系统的要求较高,而实际梯度放大器（Gradient Amplifier,GPA）有一定的限额.在有限的GPA条件下,为使得DANTE序列具有更好抑制流动信号效果,本文在读出方向以及片层旋转两个方面进行了梯度优化,实现了更好的黑血效果.     

Hepatocellular lesions with increased iron uptake on superparamagnetic iron oxide-enhanced magnetic resonance imaging in cirrhosis or chronic hepatitis: comparison of four magnetic resonance sequences for lesion conspicuity

Purpose

The aim of this study was to determine the adequate MR sequence for the lesion conspicuity of hepatocellular lesions with increased iron uptake on superparamagnetic iron oxide (SPIO)-enhanced MRI.

Materials and Methods

SPIO-enhanced MRI was performed using a 1.5-T system. Among 25 patients with hypovascular hepatocellular nodules on contrast-enhanced dynamic CT (no early enhancement at arterial phase and hypoattenuation at equilibrium phase), 39 lesions with increased iron uptake on SPIO-enhanced MRI were evaluated. SPIO-enhanced MRI included (1) T1-weighted in-phase gradient recalled echo (GRE) images, (2) T2-weighted fast spin echo (FSE) images, (3) T2*-weighted GRE with moderate TE (7 ms) and (4) long TE (12 ms). The lesion-to-liver contrast-to-noise ratios of the hepatocellular nodule and the signal-to-noise ratio (SNR) of the hepatic parenchyma were calculated by one radiologist for a quantitative assessment. MR images were reviewed retrospectively by two independent radiologists to compare the subjective lesion conspicuity in each image set based on a four-point rating scale.

Result

The mean lesion-to-liver contrast-to-noise ratios with T2*-weighted GRE with moderate TE (7 ms) was highest (5.79±3.71) and was significantly higher than those with T1-weighted, in-phase images (3.79±3.23, P<.01), T2-weighted images (2.72±1.52, P<.001) and T2*-weighted GRE with long TE (12 ms) (3.93±2.69, P<.05). The subjective rating of lesion conspicuity was best on the T2*-weighted GRE with moderate TE (7 ms), followed by that on the T2*-weighted GRE with moderate TE (7 ms; P<.05).

Conclusion

T2*-weighted GRE sequence with moderate TE (7 ms) showed high lesion-to-liver contrast-to-noise ratios in hepatocellular lesions with increased iron uptake on SPIO-enhanced MRI, indicating better lesion conspicuity of hypointense hepatocellular nodules in cirrhosis or chronic hepatitis.     

Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.     

The use of T2*-weighted multi-echo GRE imaging as a novel method to diagnose hepatocellular carcinoma compared with gadolinium-enhanced MRI: a feasibility study

Background

The goal of the study was to assess a T2*-weighted MRI sequence for the ability to identify hepatocellular carcinoma (HCC).

Methods

Hepatic iron deposition, which is common in chronic liver disease (CLD), may increase the conspicuity of HCC on GRE imaging due to increased T2* signal decay in liver parenchyma. In this study, a breath-hold T2*-weighted MRI sequence was evaluated by a blinded observer for HCC and the results compared to a reference standard of gadolinium-enhanced MRI in these same patients. Forty-one patients (mean age 56.2 years; 17 females) were included in this approved, retrospective study.

Results

By the reference standard, 14 of 41 patients had a total of 25 HCCs. The sensitivity of the T2*-weighted MR sequence for identifying HCC, per lesion, was 60%, while the specificity was 100%. There was a significantly lower T2* value of liver parenchyma in patients with HCC identified by the T2*-weighted sequence than in those with HCCs which were not identified by the T2*-weighted sequence (27.8±2.2 vs. 21.9±2.1 ms; P=.02).

Conclusions

A T2*-weighted MRI sequence can identify HCC in patients with CLD. This technique may be beneficial for imaging of patients contraindicated for gadolinium.     

Inversion recovery ultrashort echo time magnetic resonance imaging: A method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain – A feasibility study

Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (< 1 ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3 T scanner. The technique was first validated on a synthetic myelin phantom (myelin powder in D₂O) and a Feridex iron phantom. This was followed by studies of cadaveric MS specimens, healthy volunteers and MS patients. UTE imaging of the synthetic myelin phantom showed an excellent bi-component signal decay with two populations of protons, one with a T2* of 1.2 ms (residual water protons) and the other with a T2* of 290 μs (myelin protons). IR-UTE imaging shows sensitivity to a wide range of iron concentrations from 0.5 to ~ 30 mM. The IR-UTE signal from white matter of the brain of healthy volunteers shows a rapid signal decay with a short T2* of ~ 300 μs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter.     

Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T

The objective of this study was to implement a clinically relevant multi-slice multi-echo imaging sequence in order to quantify multi-component T2 relaxation times for normal volunteers at both 1.5 and 3 T. Multi-echo data were fitted using a nonnegative least square algorithm. Twelve echo data with nonlinear echo sampling were acquired using a receive-only eight-channel phased array coil and volume head coil for phantoms and normal volunteers, and compared to 32-echo data with linear echo sampling. It was observed that the performance of the 180 degrees refocusing trains was more spatially uniform for the receive-only eight-channel phased array coil than for the head coil, particularly at 3 T. The phantom study showed that the estimated T2 relaxation times were accurate and reproducible for both single- and multi-slice acquisition from a commercial phantom with known T2 relaxation times. Short T2 components (T2 <50 ms) were mainly observed within the white matter for normal volunteers, and the fraction of short T2 water components (i.e., myelin water) was 7-12% of total water. It was observed that the calculated myelin water fraction map from the nonlinearly sampled 12-echo data was comparable with that from the linearly sampled 32-echo data. Quantification of T2 relaxation times from multi-slice images was accomplished with a clinically acceptable scan times (16 min) for normal volunteers by using a nonselective T2 prep imaging sequence. The use of the eight-channel head coil involved more accurate quantification of T2 relaxation times particularly when the number of echoes was limited.     

The impact of spin coupling signal loss on fat content characterization in multi-echo acquisitions with different echo spacing

PurposeThis study aimed to assess the effect of echo spacing in transverse magnetization (T2) signal decay of gel and fat (oil) samples. Additionally, we assess the feasibility of using spin coupling as a determinant of fat content.MethodsPhantoms of known T2 values, as well as vegetable oil phantoms, were scanned at 1.5 T scanner with a multi echo FSE sequence of variable echo spacing above and below the empirical threshold of 20 ms for echo train signal modulation (6.7, 13.6, 26.8, and 40 ms). T2 values were calculated from monoexponential fitting of the data. Relative signal loss between the four acquisitions of different echo spacing was calculated.ResultsAgreement in the T2 values of water gel phantom was observed in all acquisitions as opposed to fat phantom (oil) samples. Relative differences in signal intensity between two successive sequences of different echo spacing on composite fat/water regions of interest was found to be linearly correlated to fat fraction of the ROI.ConclusionThe sample specific degree of signal loss that was observed between different fat samples (vegetable oils) can be attributed to the composition of each sample in J coupled fat components. Hence, spin coupling may be used as a determinant of fat content.     

APIR4EMC: Autocalibrated parallel imaging reconstruction for extended multi-contrast imaging

PurposeTo improve image quality of multi-contrast imaging with the proposed Autocalibrated Parallel Imaging Reconstruction for Extended Multi-Contrast Imaging (APIR4EMC).MethodsAPIR4EMC reconstructs multi-contrast images in an autocalibrated parallel imaging reconstruction framework by adding contrasts as virtual coils. Compensation of signal evolution along the echo train of different contrasts is performed to improve signal prediction for missing samples. As a proof of concept, we performed prospectively accelerated phantom and in-vivo brain acquisitions with T1, T1-fat saturated (Fatsat), T2, PD, and FLAIR contrasts. The k-space sampling patterns of these acquisitions were jointly optimized. Images were jointly reconstructed with the proposed APIR4EMC method as well as individually with GRAPPA. Root mean square error (RMSE) to fully sampled reference images and g-factor maps were computed for both methods in the phantom experiment. Visual evaluation was performed in the in-vivo experiment.ResultsCompared to GRAPPA, APIR4EMC reduced artifacts and improved SNR of the reconstructed images in the phantom acquisitions. Quantitatively, APIR4EMC substantially reduced noise amplification (g-factor) as well as RMSE compared to GRAPPA. Signal evolution compensation reduced artifacts. In the in-vivo experiments, 1 mm³ isotropic 3D images with contrasts of T1, T1-Fatsat, T2, PD, and FLAIR were acquired in as little as 7.5 min with the acceleration factor of 9. Reconstruction quality was consistent with the phantom results.ConclusionCompared to single contrast reconstruction with GRAPPA, APIR4EMC reduces artifacts and noise amplification in accelerated multi-contrast imaging.     

In vivo hypoxia characterization using blood oxygen level dependent magnetic resonance imaging in a preclinical glioblastoma mouse model

PurposeHypoxia measurements can provide crucial information regarding tumor aggressiveness, however current preclinical approaches are limited. Blood oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) has the potential to continuously monitor tumor pathophysiology (including hypoxia). The aim of this preliminary work was to develop and evaluate BOLD MRI followed by post-image analysis to identify regions of hypoxia in a murine glioblastoma (GBM) model.MethodsA murine orthotopic GBM model (GL261-luc2) was used and independent images were generated from multiple slices in four different mice. Image slices were randomized and split into training and validation cohorts. A 7 T MRI was used to acquire anatomical images using a fast-spin-echo (FSE) T2-weighted sequence. BOLD images were taken with a T2*-weighted gradient echo (GRE) and an oxygen challenge. Thirteen images were evaluated in a training cohort to develop the MRI sequence and optimize post-image analysis. An in-house MATLAB code was used to evaluate MR images and generate hypoxia maps for a range of thresholding and ΔT2* values, which were compared against respective pimonidazole sections to optimize image processing parameters. The remaining (n = 6) images were used as a validation group. Following imaging, mice were injected with pimonidazole and collected for immunohistochemistry (IHC). A test of correlation (Pearson's coefficient) and agreement (Bland-Altman plot) were conducted to evaluate the respective MRI slices and pimonidazole IHC sections.ResultsFor the training cohort, the optimized parameters of “thresholding” (20 ≤ T2* ≤ 35 ms) and ΔT2* (±4 ms) yielded a Pearson's correlation of 0.697. These parameters were applied to the validation cohort confirming a strong Pearson's correlation (0.749) when comparing the respective analyzed MR and pimonidazole images.ConclusionOur preliminary study supports the hypothesis that BOLD MRI is correlated with pimonidazole measurements of hypoxia in an orthotopic GBM mouse model. This technique has further potential to monitor hypoxia during tumor development and therapy.     

A fast method for the quantification of fat fraction and relaxation times: Comparison of five sites of bone marrow

PurposeBone marrow is found either as red bone marrow, which mainly contains haematopoietic cells, or yellow bone marrow, which mainly contains adipocytes. In adults, red bone marrow is principally located in the axial skeleton. A recent study has introduced a method to simultaneously estimate the fat fraction (FF), the T1 and T2* relaxation times of water (T1w, T2*w) and fat (T1f and T2*f) in the vertebral bone marrow. The aim of the current study was to measure FF, T1w, T1f, T2*w and T2*f in five sites of bone marrow, and to assess the presence of regional variations.MethodsMRI experiments were performed at 1.5 T on five healthy volunteers (31.6 ± 15.6 years) using a prototype chemical-shift-encoded 3D multi-gradient-echo sequence (VIBE) acquired with two flip angles. Acquisitions were performed in the shoulders, lumbar spine and pelvis, with acquisition times of < 25 seconds per sequence. Signal intensities of magnitude images of the individual echoes were used to fit the signal and compute FF, T1w, T1f, T2*w and T2*f in the humerus, sternum, vertebra, ilium and femur.ResultsRegional variations of fat fraction and relaxation times were observed in these sites, with higher fat fraction and longer T1w in the epiphyses of long bones. A high correlation between FF and T1w was measured in these bones (R = 0.84 in the humerus and R = 0.84 in the femur). In most sites, there was a significant difference between water and fat relaxation times, attesting the relevance of measuring these parameters separately.ConclusionThe method proposed in the current study allowed for measurements of FF, T1w, T1f, T2*w and T2*f in five sites of bone marrow. Regional variations of these parameters were observed and a strong negative correlation between the T1 of water and the fat fraction in bones with high fat fractions was found.     

In vivo GABA detection with improved selectivity and sensitivity by localized double quantum filter technique at 4.1T

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter for the normal function of mammal and human brain. It is difficult to detect GABA signal with the conventional single quantum technique due to its relatively low concentration and overlapping with other signals from creatine (Cr), glutathione (GSH), as well as macromolecules. Using a high-selective read pulse, DANTE, and at the facility of increased sensitivity and chemical shift resolution at high-field 4.1T, GABA editing by double quantum filter (DQF) with robust suppression of Cr and GSH was achieved. Our editing efficiency of 40-50% was achievable on a GABA phantom (50 mM GABA and 61 mM choline). Furthermore, GABA editing spectra were acquired with echo time TE = 77 ms, and any possible macromolecular contamination to GABA editing spectra was found to be negligible. This high-field DQF setup was applied to 11 healthy volunteers, and the mean GABA level was measured to be 1.12 +/- 0.15 mM in the occipital lobe in reference to 7.1 mM Cr concentration.     

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study

In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2 water protons. Magnitude and phase imaging and T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D₂O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ~ 300 μs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from − 7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTE sequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.     

Effectiveness Evaluation of the Fat Percentage Determination in Multi-Echo T2-Corrected Single-Voxel Spectroscopy by Comparing the 3-Point Dixon and the 6-Point Interference Dixon Techniques

This study compared fat percentage in the HISTO method and chemical-shift imaging method, a 3-echo 3D gradient echo sequence with a T2*-corrected Dixon (3-point Dixon) and 6-echo interference Dixon magnetic resonance (MR) imaging (6-point Dixon) method, to evaluate clinical significance of fatty liver quantification by multi-echo T2*-corrected single-voxel spectroscopy Histo (HISTO). A total of 21 liver donors underwent MR imaging examination. The 3-T MR system (Siemens Healthcare Tim Verio, Erlangen, Germany) was used for all studies. For fat percentage evaluations, a 3-echo 3D gradient echo sequence with T2*-corrected Dixon (3-point Dixon) and 6-Echo Interference Dixon (6-point Dixon) pulse sequences, including HISTO, were applied in sequence. Using fat percentages obtained from each pulse sequence, levels of fatty liver were classified as: non-fatty liver, <5 %; mild fatty liver, >5 but <31 %; and severe fatty liver, >31 %. The correlation between methods was calculated with a correlation coefficient (R ²): HISTO and 3-point Dixon, 0.936 (p < 0.001); HISTO and 6-point Dixon, 0.944 (p < 0.001); and 3-point Dixon and 6-point Dixon, 0.984 (p < 0.001). The HISTO, which was used to investigate fat percentages after T2* correction, showed a high correlation with 3-point Dixon and 6-point Dixon, suggesting that the multi-echo method is useful for accurately determining fat percentages.