The Aging Imageomics Study: rationale, design and baseline characteristics of the study population.

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged ≥50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

Novel axolotl cardiac function analysis method using magnetic resonance imaging.

The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function of axolotls. Three axolotls were imaged with magnetic resonance imaging using a retrospectively gated Fast Low Angle Shot cine sequence. Within one scanning session the axolotl heart was imaged three times in all planes, consecutively. Heart rate, ejection fraction, stroke volume and cardiac output were calculated using three techniques: (1) combined long-axis, (2) short-axis series, and (3) ultrasound (control for heart rate only). All values are presented as mean ± standard deviation. Heart rate (beats per minute) among different animals was 32.2±6.0 (long axis), 30.4±5.5 (short axis) and 32.7±4.9 (ultrasound) and statistically similar regardless of the imaging method (p > 0.05). Ejection fraction (%) was 59.6±10.8 (long axis) and 48.1±11.3 (short axis) and it differed significantly (p = 0.019). Stroke volume (µl/beat) was 133.7±33.7 (long axis) and 93.2±31.2 (short axis), also differed significantly (p = 0.015). Calculations were consistent among the animals and over three repeated measurements. The heart rate varied depending on depth of anaesthesia. We described a new method for defining and imaging the anatomical planes of the axolotl heart and propose one of our techniques (long axis analysis) may prove useful in defining cardiac function in regenerating axolotl hearts.

Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

Determinants of iron accumulation in deep grey matter of multiple sclerosis patients.

BACKGROUND: Iron accumulation in deep grey matter (GM) structures is a consistent finding in multiple sclerosis (MS) patients. This study focused on the identification of independent determinants of iron accumulation using R2* mapping. SUBJECTS AND METHODS: Ninety-seven MS patients and 81 healthy controls were included in this multicentre study. R2* mapping was performed on 3T MRI systems. R2*in deep GM was corrected for age and was related to disease duration, disability, T2 lesion load and brain volume. RESULTS: Compared to controls, R2* was increased in all deep GM regions of MS patients except the globus pallidus and the substantia nigra. R2* increase was most pronounced in the progressive stage of the disease and independently predicted by disease duration and disability. Reduced cortical volume was not associated with iron accumulation in the deep GM with the exception of the substantia nigra and the red nucleus. In lesions, R2* was inversely correlated with disease duration and higher total lesion load. CONCLUSION: Iron accumulation in deep GM of MS patients is most strongly and independently associated with duration and severity of the disease. Additional associations between cortical GM atrophy and deep GM iron accumulation appear to exist in a region specific manner.

Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics.

Recently, a new MRI technique was developed at 3 Tesla (T), called fluid attenuated inversion recovery* (FLAIR*). In this study, we implemented FLAIR* in an existing MS cohort at 7 T, to investigate whether we could corroborate results of previous 7 T studies that introduced specific MS lesion characteristics. Furthermore, we aimed to investigate the meaning of these lesion characteristics by relating them to clinical characteristics of the MS patient. Three-dimensional FLAIR and T2*-weighted images of 33 MS patients and 7 healthy controls were fused into FLAIR* images. Lesion type, signal intensity and morphology were analysed on FLAIR*, side-by-side with the original FLAIR and T2*, and correlated with clinical characteristics using Spearman's rho. Three morphological features of MS lesions were visualised: (1) central vessel (CV) within lesions, present in 78 % of total MS lesions; (2) hypointense rims around MS lesions, present in eight patients; (3) FLAIR* lesions that were hypointense at T2*, present in 13 patients. The presence of hypointense (rims around) lesions was not related to clinical characteristics. The simultaneous presence of rimlike lesions and hypointense lesions within MS patients was significantly correlated (ρ = 0.52, P < 0.01). We conclude that the implementation of the new MRI technique FLAIR* at ultra-high-field 7 T combines and corroborates the results of preceding 7 T research, by showing three morphological features of MS lesions. In addition, our study shows that these phenomena do not show a relation to patient's clinical characteristics and cannot be allocated to certain MS disease subtypes.

Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla.

OBJECTIVES: To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T). METHODS: We examined 16 MS patients and 16 age-matched patients with (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were combined into FLAIR* images. Lesion type and intensity, perivascular orientation and presence of a hypointense rim were analysed. RESULTS: In total, 433 cerebral lesions were detected in MS patients versus 86 lesions in vascular patients. Lesions in MS patients were significantly more often orientated in a perivascular manner: 74 % vs. 47 % (P < 0.001). Ten MS lesions (2.3 %) were surrounded by a hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No lesions in vascular patients showed any rim or hypointensity. Specificity of differentiating MS from vascular lesions on 7-T FLAIR* increased when the presence of a central vessel was taken into account (from 63 % to 88 %), most obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity remained (81 %). CONCLUSION: 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions. KEY POINTS: • A new MRI technique T2*-weighted fluid attenuation inversion recovery (FLAIR*) was investigated. • FLAIR* at 7-T MRI combines FLAIR and T2* images into a single image. • FLAIR* at 7 T does not require enhancement with contrast agents. •High-resolution 7-T FLAIR* improves differentiation between MS and vascular brain lesions. • FLAIR* revealed a central vessel more frequently in MS than vascular lesions.

Clinical application of multi-contrast 7-T MR imaging in multiple sclerosis: increased lesion detection compared to 3 T confined to grey matter.

OBJECTIVES: Seven-Tesla MRI demonstrated new pathological features of multiple sclerosis (MS) using T2-weighted sequences. However, a clinical MRI protocol at 7 T has never been investigated. We evaluated the clinical value of 7-T MRI by investigating the sensitivity of lesion detection compared with 3 T. METHODS: Thirty-eight MS patients and eight healthy controls underwent multi-contrast MRI using 3D T1-weighted (3D-T1w), 2D dual-echo T2-weighted (2D-T2w) and 3D fluid-attenuated inversion recovery (3D-FLAIR) at 3 and 7 T. Images were analysed for focal lesions, which were counted and categorised according to anatomical location. The study was approved by the institutional review board. RESULTS: Lesion-wise analysis showed increased lesion counts in cortical grey matter (GM) at 7 T of 91, 75 and 238 % for 3D-T1w, 2D-T2w and FLAIR sequences, respectively. Patient-wise analysis confirmed this for 2D-T2w and FLAIR (P < 0.023 and P < 0.001). Seven-Tesla white matter (WM) lesion detection was not increased; 3D-FLAIR even detected significantly more WM lesions at 3 T. CONCLUSIONS: Using a clinical multi-contrast MRI protocol, increased lesion detection was observed in cortical GM but not in WM. Given the clinical relevance of GM abnormalities, this may have consequences for clinical outcome measures, prognostic classification and future diagnostic criteria incorporating GM abnormalities.

Inflammation high-field magnetic resonance imaging.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). MS has been subject to high-field magnetic resonance (MR) imaging research to a great extent during the past years, and much data has been collected that might be helpful in the investigation of other inflammatory CNS disorders. This article reviews the value of high-field MR imaging in examining inflammatory MS abnormalities. Furthermore, possibilities and challenges for the future of high-field MR imaging in MS are discussed.

Lesion detection at seven Tesla in multiple sclerosis using magnetisation prepared 3D-FLAIR and 3D-DIR.

OBJECTIVES: To examine the feasibility and value of 7 T 3D T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) and Double Inversion Recovery (DIR) MR sequences for lesion detection in multiple sclerosis (MS). METHODS: High-resolution 3D-FLAIR and 3D-DIR MR sequences at 7 T were obtained using magnetisation preparation (MP), and compared with 2D-T2-weighted and 3D-T1-weighted sequences in 10 MS patients and five healthy controls. We determined contrast ratios and counted lesions according to anatomical location. RESULTS: MR imaging at 7 T was safe and allowed multi-contrast imaging within clinically acceptable imaging times. Lesion to white matter (WM) and grey matter (GM) contrast ratios were higher in 3D-MP-FLAIR and 3D-MP-DIR compared with 2D-T2 and 3D-T1. Cortical (mixed+intra-cortical) and total lesion counts were 97/592 on 3D-MP-FLAIR and 100/558 on 3D-MP-DIR compared with 84/384 on 2D-T2 and 42/442 on 3D-T1. More juxta-cortical lesions were seen with 3D-MP-FLAIR (205) and 3D-MP-DIR (133) than with 2D-T2 (125) and 3D-T1 (70). Finally, higher numbers of lesions were found for deep WM lesions: 176 for 3D-MP-FLAIR and 196 for 3D-MP-DIR vs. 155 for 2D-T2 and 131 for 3D-T1. CONCLUSIONS: Near isotropic 3D-MP-FLAIR and 3D-MP-DIR allows high quality T2-weighted MR imaging in MS at 7 T, improving (cortical) lesion detection.

MRI assessment of iron deposition in multiple sclerosis.

Iron deposition in the human brain tissue occurs in the process of normal aging and in many neurodegenerative diseases. Elevated iron levels in certain brain regions are also an increasingly recognized finding in multiple sclerosis (MS). The exact mechanism(s) for this phenomenon and its implication in terms of pathophysiology and clinical significance are still largely unknown and debated. Reliable methods to exactly quantify brain iron are a first step to clarify these issues. Therefore, the aim of this review is to present currently available magnetic resonance imaging (MRI) techniques for the assessment of brain iron. These include relaxation time mapping, phase imaging, susceptibility-weighted imaging, susceptibility mapping, magnetic field correlation imaging, and direct saturation imaging. After discussing their advantages and disadvantages, existing MRI clinical correlations with brain iron concentration in MS are summarized and future research directions are shown.

No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study.

BACKGROUND: Recent studies using colour-coded Doppler sonography showed that chronic impaired venous drainage from the central nervous system is almost exclusively found in multiple sclerosis (MS) patients. This study aimed to investigate the intracranial and extracranial venous anatomy and the intracerebral venous flow profile in patients with MS and healthy controls using magnetic resonance venography (MRV). METHODS: Twenty patients with definite MS and 20 age- and gender-matched healthy controls were examined. MR imaging was performed on a whole-body 3T MR system including both 3D phase-contrast and dynamic 3D contrast-enhanced MRV as well as flow quantification of the internal cerebral veins and the straight sinus. Image analysis was performed by two experienced interventional neuroradiologists blinded to clinical data and structural brain imaging. The intracranial and extracranial neck veins were analysed for stenosis/occlusion and alternative venous drainage pattern. RESULTS: A completely normal venous anatomy was observed in 10 MS patients and 12 controls. Anomalies of the venous system (venous stenosis/occlusions) were found in 10 MS patients and eight healthy controls. An anomalous venous system in combination with associated alternative venous drainage was observed in six MS patients and five healthy controls. Flow quantification showed no venous backflow in any MS patient or control. CONCLUSIONS: Findings suggestive of anomalies of the cranial venous outflow anatomy were frequently observed in both MS patients and healthy controls. Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions.

Comparison between prospective and retrospective triggering for mouse cardiac MRI.

High-resolution magnetic resonance imaging (MRI) has evolved into one of the major non-invasive tools to study the healthy and diseased mouse heart. This study presents a Cartesian CINE MRI protocol based on a fast low-angle shot sequence with a navigator echo to generate cardiac triggering and respiratory gating signals retrospectively, making the use of ECG leads and respiratory motion sensors obsolete. MRI of the in vivo mouse heart using this sequence resulted in CINE images with no detectable cardiac and respiratory motion artefacts. The retrospective method allows for steady-state imaging of the mouse heart, which is essential for quantitative contrast-enhanced MRI studies. A comparison was made between prospective and retrospective methods in terms of the signal-to-noise ratio and the contrast-to-noise ratio between blood and myocardial wall, as well as global cardiac functional indices: end-diastolic volume, end-systolic volume, stroke volume and ejection fraction. The retrospective method resulted in almost constant left-ventricle wall signal intensity throughout the cardiac cycle, at the expense of a decrease in the signal-to-noise ratio and the contrast-to-noise ratio between blood and myocardial wall as compared with the prospective method. Prospective and retrospective sequences yielded comparable global cardiac functional indices. The largest mean relative difference found was 8% for the end-systolic volume.