Patients with knee osteoarthritis can be divided into subgroups based on tibiofemoral joint kinematics of gait - an exploratory and dynamic radiostereometric study.

OBJECTIVE: Patients with advanced knee osteoarthritis (KOA) frequently alter their gait patterns in an attempt to alleviate symptoms. Understanding the underlying pathomechanics and identifying KOA phenotypes are essential to improve treatments. We investigated kinematics in patients with KOA to identify subgroups of homogeneous knee joint kinematics. METHOD: A total of 66 patients with symptomatic KOA scheduled for total knee arthroplasty and 15 age-matched healthy volunteers with asymptomatic, non-arthritic knees were included. We used k-means clustering to divide patients into subgroups based on dynamic radiostereometry-assessed tibiofemoral joint kinematics. Clinical characteristics such as knee ligament lesions and KOA scores were graded by magnetic resonance imaging and radiographs, respectively. RESULTS: We identified four clusters that were supported by clinical characteristics. The flexion group (n = 20) consisted primarily of patients with medial KOA. The abduction group (n = 17) consisted primarily of patients with lateral KOA. The anterior draw group (n = 10) was composed of patients with medial KOA, some degree of anterior cruciate ligament lesion and the highest KOA score. The external rotation group (n = 19) primarily included patients with medial collateral and posterior cruciate ligament lesions. CONCLUSION: Based on tibiofemoral gait patterns, patients with advanced KOA can be divided into four subgroups with specific clinical characteristics and different KOA-affected compartments. The findings add to our understanding of how knee kinematics may affect the patient's development of different types of KOA. This may inspire improved and more patient-specific treatment strategies in the future.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy.

OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (VCSF) and the T2 of CSF (T2,CSF) was calculated. The correlation between VCSF/T2,CSF and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. RESULTS: Relative total, peripheral subarachnoidal, and ventricular VCSF increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T2 of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). CONCLUSION: A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T2 of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. KEY POINTS: • A 1:11 min CSF MRI volumetric sequence can evaluate brain atrophy. • CSF MRI provides accurate atrophy assessment without partial volume effects. • CSF MRI data can be processed quickly without user interaction. • The measured T 2 of the CSF is related to brain atrophy.

Multi-vendor reliability of arterial spin labeling perfusion MRI using a near-identical sequence: implications for multi-center studies.

INTRODUCTION: A main obstacle that impedes standardized clinical and research applications of arterial spin labeling (ASL), is the substantial differences between the commercial implementations of ASL from major MRI vendors. In this study, we compare a single identical 2D gradient-echo EPI pseudo-continuous ASL (PCASL) sequence implemented on 3T scanners from three vendors (General Electric Healthcare, Philips Healthcare and Siemens Healthcare) within the same center and with the same subjects. MATERIAL AND METHODS: Fourteen healthy volunteers (50% male, age 26.4±4.7years) were scanned twice on each scanner in an interleaved manner within 3h. Because of differences in gradient and coil specifications, two separate studies were performed with slightly different sequence parameters, with one scanner used across both studies for comparison. Reproducibility was evaluated by means of quantitative cerebral blood flow (CBF) agreement and inter-session variation, both on a region-of-interest (ROI) and voxel level. In addition, a qualitative similarity comparison of the CBF maps was performed by three experienced neuro-radiologists. RESULTS: There were no CBF differences between vendors in study 1 (p>0.1), but there were CBF differences of 2-19% between vendors in study 2 (p<0.001 in most gray matter ROIs) and 10-22% difference in CBF values obtained with the same vendor between studies (p<0.001 in most gray matter ROIs). The inter-vendor inter-session variation was not significantly larger than the intra-vendor variation in all (p>0.1) but one of the ROIs (p<0.001). CONCLUSION: This study demonstrates the possibility to acquire comparable cerebral CBF maps on scanners of different vendors. Small differences in sequence parameters can have a larger effect on the reproducibility of ASL than hardware or software differences between vendors. These results suggest that researchers should strive to employ identical labeling and readout strategies in multi-center ASL studies.

Age-related changes in brain hemodynamics; A calibrated MRI study.

INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2 ). To clarify the effects of these physiological parameters, we investigated the effect of age on baseline CBF and CMRO2 . MATERIALS AND METHODS: Twenty young (mean ± sd age, 28 ± 3 years), and 45 older subjects (66 ± 4 years) were investigated. A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P < 0.05). Age-related differences in CBF decreased to the point of nonsignificance (B=-4.1, SE=3.8) when EtCO2 was added as a confounder. BOLD CVR was lower in the whole brain, in the frontal, in the temporal, and in the occipital of the older subjects (P<0.05). Whole brain OEF was 43 ± 8% in the young and 39 ± 6% in the older subjects (P = 0.066). Whole brain CMRO2 was 181 ± 60 and 133 ± 43 µmol/100 g/min in young and older subjects, respectively (P<0.01). DISCUSSION: Age-related differences in CBF could potentially be explained by differences in EtCO2 . Regional CMRO2 was lower in older subjects. BOLD studies should take this into account when investigating age-related changes in neuronal activity.

Simultaneous quantitative assessment of cerebral physiology using respiratory-calibrated MRI and near-infrared spectroscopy in healthy adults.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) and functional MRI (fMRI) are non-invasive techniques used to relate activity in different brain regions to certain tasks. Respiratory calibration of the blood oxygen level dependent (BOLD) signal, and combined fNIRS-fMRI approaches have been used to quantify physiological subcomponents giving rise to the BOLD signal. A comparison of absolute oxygen metabolism parameters between MRI and NIRS, using spatially resolved (SRS) NIRS and respiratory calibrated MRI, could yield additional insight in the physiology underlying activation. MATERIALS AND METHODS: Changes in the BOLD signal, cerebral blood flow (CBF), and oxygen saturation (SO2) were derived from a single MRI sequence during a respiratory challenge in healthy volunteers. These changes were compared to SO2 obtained by a single probe SRS NIRS setup. In addition, concentration changes in oxygenated (O2Hb), deoxygenated (HHb), and total haemoglobin (tHb), obtained by NIRS, were compared to the parameters obtained by MRI. RESULTS: NIRS SO2 correlated with end-tidal CO2 (0.83, p<0.0001), the BOLD signal (0.82, p<0.0001), CBF (0.85, p<0.0001), and also MRI SO2 (0.82, p<0.0001). The BOLD signal correlated with NIRS HHb (-0.76, p<0.0001), O2Hb (0.41, p=0.001), and tHb (r=0.32, p=0.01). CONCLUSIONS: Good correlations show that changes in cerebral physiology, following a respiratory challenge, go hand in hand with changes in the BOLD signal, CBF, O2Hb, HHb, NIRS SO2, and MRI SO2. Out of all NIRS derived parameters, the SO2 showed the best correlation with the BOLD signal.

Non-invasive MRI measurements of venous oxygenation, oxygen extraction fraction and oxygen consumption in neonates.

BACKGROUND AND PURPOSE: Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a non-invasive MRI method to evaluate whole brain oxygen consumption in neonates. MATERIALS AND METHODS: For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the 'T2 prepared tissue relaxation inversion recovery' pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements. RESULTS: Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12µmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic-ischemic encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01, respectively) with postnatal age. CONCLUSION: We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurement techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹5O H2O positron emission tomography.

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H2O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H2O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H2O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.

In vivo blood T(1) measurements at 1.5 T, 3 T, and 7 T.

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal-to-noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra-high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look-Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal-to-noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed.

MR regional perfusion imaging: visualizing functional collateral circulation.

SUMMARY: We applied regional perfusion imaging (RPI), a new arterial spin-labeling MR imaging method that selectively studies regions of the brain perfused by individual carotid and basilar arteries. In a patient with cerebrovascular disease, RPI showed cerebral tissue perfused by pial collateral vessels, thereby demonstrating the relationship between anatomic and functional information, which was lacking in conventional x-ray angiography. RPI may be useful to study functional collateral circulation and hence guide therapy in ischemic disease.

Cerebral ventricular size in the offspring of schizophrenic mothers. A preliminary study.

Within a prospective, longitudinal study of offspring of schizophrenic mothers, computed tomographic scan-derived measurements of ventricular size were evaluated for a subsample consisting of schizophrenics, borderline schizophrenics (DSM-III schizotypal), and mentally healthy individuals. Schizophrenics exhibited larger ventricular sizes and borderline schizophrenics smaller ventricular sizes than mentally healthy individuals. Ventricular size correlated with premorbidly obtained obstetric data. These results are interpreted as being consistent with the hypothesis that neurological insult may decompensate schizotypal individuals toward florid schizophrenia.

Cerebral Perfusion Measurements in Elderly with Hypertension Using Arterial Spin Labeling.

PURPOSE: The current study assesses the feasibility and value of crushed cerebral blood flow (CBFcrushed) and arterial transit time (ATT) estimations for large clinical imaging studies in elderly with hypertension. MATERIAL AND METHODS: Two pseudo-continuous arterial spin labeling (ASL) scans with (CBFcrushed) and without flow crushers (CBFnon-crushed) were performed in 186 elderly with hypertension, from which CBF and ATT maps were calculated. Standard flow territory maps were subdivided into proximal, intermediate and distal flow territories, based on the measured ATT. The coefficient of variation (CV) and physiological correlations with age and gender were compared between the three perfusion parameters. RESULTS: There was no difference in CV between CBFcrushed and CBFnon-crushed (15-24%, p>0.4) but the CV of ATT (4-9%) was much smaller. The total gray matter correlations with age and gender were most significant with ATT (p = .016 and p<.001 respectively), in between for CBFcrushed (p = .206 and p = .019) and least significant for CBFnon-crushed (p = .236 and p = .100). CONCLUSION: These data show the feasibility and added value of combined measurements of both crushed CBF and ATT for group analyses in elderly with hypertension. The obtained flow territories provide knowledge on vascular anatomy of elderly with hypertension and can be used in future studies to investigate regional vascular effects.

Impact of neonate haematocrit variability on the longitudinal relaxation time of blood: Implications for arterial spin labelling MRI.

BACKGROUND AND PURPOSE: The longitudinal relaxation time of blood (T 1b) is influenced by haematocrit (Hct) which is known to vary in neonates. The purpose of this study was threefold: to obtain T 1b values in neonates, to investigate how the T 1b influences quantitative arterial spin labelling (ASL), and to evaluate if known relationships between T 1b and haematocrit (Hct) hold true when Hct is measured by means of a point-of-care device. MATERIALS AND METHODS: One hundred and four neonates with 120 MR scan sessions (3 T) were included. The T 1b was obtained from a T 1 inversion recovery sequence. T 1b-induced changes in ASL cerebral blood flow estimates were evaluated. The Hct was obtained by means of a point-of-care device. Linear regression analysis was used to investigate the relation between Hct and MRI-derived R1 of blood (the inverse of the T 1b). RESULTS: Mean T 1b was 1.85 s (sd 0.2 s). The mean T 1b in preterm neonates was 1.77 s, 1.89 s in preterm neonates scanned at term-equivalent age (TEA) and 1.81 s in diseased neonates. The T 1b in the TEA was significantly different from the T 1b in the preterm (p < 0.05). The change in perfusion induced by the T 1b was -11% (sd 9.1%, p < 0.001). The relation between arterial-drawn Hct and R1b was R1b = 0.80 × Hct + 0.22, which falls within the confidence interval of the previously established relationships, whereas capillary-drawn Hct did not correlate with R1b. CONCLUSION: We demonstrated a wide variability of the T 1b in neonates and the implications it could have in methods relying on the actual T 1b as for instance ASL. It was concluded that arterial-drawn Hct values obtained from a point-of-care device can be used to infer the T 1b whereas our data did not support the use of capillary-drawn Hct for T 1b correction.

Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques.

The non-invasive nature of arterial spin labelling (ASL) has opened a unique window into human brain function and perfusion physiology. High spatial and temporal resolution makes the technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience where the aim is to develop a more comprehensive picture of the physiological events accompanying neuronal activation. However, low signal-to-noise ratio and the complexity of flow quantification make ASL one of the more demanding disciplines within MRI. In this review, the theoretical background and main implementations of ASL are revisited. In particular, the perfusion quantification methods, including the problems and pitfalls involved, are thoroughly discussed in this article. Finally, a brief summary of applications is provided.