High inspired CO2 target accuracy in mechanical ventilation and spontaneous breathing using the Additional CO2 method.

Introduction: Cerebrovascular reactivity imaging (CVR) is a diagnostic method for assessment of alterations in cerebral blood flow in response to a controlled vascular stimulus. The principal utility is the capacity to evaluate the cerebrovascular reserve, thereby elucidating autoregulatory functioning. In CVR, CO2 gas challenge is the most prevalent method, which elicits a vascular response by alterations in inspired CO2 concentrations. While several systems have been proposed in the literature, only a limited number have been devised to operate in tandem with mechanical ventilation, thus constraining the majority CVR investigations to spontaneously breathing individuals. Methods: We have developed a new method, denoted Additional CO2, designed to enable CO2 challenge in ventilators. The central idea is the introduction of an additional flow of highly concentrated CO2 into the respiratory circuit, as opposed to administration of the entire gas mixture from a reservoir. By monitoring the main respiratory gas flow emanating from the ventilator, the CO2 concentration in the inspired gas can be manipulated by adjusting the proportion of additional CO2. We evaluated the efficacy of this approach in (1) a ventilator coupled with a test lung and (2) in spontaneously breathing healthy subjects. The method was evaluated by assessment of the precision in attaining target inspired CO2 levels and examination of its performance within a magnetic resonance imaging environment. Results and discussion: Our investigations revealed that the Additional CO2 method consistently achieved a high degree of accuracy in reaching target inspired CO2 levels in both mechanical ventilation and spontaneous breathing. We anticipate that these findings will lay the groundwork for a broader implementation of CVR assessments in mechanically ventilated patients.

Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging.

OBJECTIVE: Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity. METHODS: Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool. RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone. CONCLUSIONS: The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.

MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up.

There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41-79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46-69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence (Cc) and variance in compartment's size (CMD) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences (P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and Cc were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and CMD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and CMD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in Cc were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to Cc, the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and CMD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19.

Radiation-dependent demyelination in normal appearing white matter in glioma patients, determined using quantitative magnetic resonance imaging.

Background and purpose: A brain tumour, especially a glioma, is a rare disease; it is challenging to treat and the prognosis is often poor. Routine care includes surgery and concomitant chemoradiotherapy (CRT). Diagnostic work-up and treatment effects are typically evaluated using magnetic resonance imaging (MRI). Quantitative MRI (qMRI), unlike conventional MRI, has the advantage of providing tissue-specific relaxation rates and proton density. The purpose is to detect changes in normal appearing white matter (NAWM) in brain tumour patients after CRT using qMRI. Materials & methods: NAWM was analysed in 10 patients, in 83 MR examinations performed before and after surgery and after CRT. Relaxation rates R1 and R2, the proton density (PD) and the concentration of myelin (cMy) were calculated from the qMRI scans and analysed in correlation to radiation dose and time after treatment. Results: A significant decrease in cMy between pre-treatment imaging and first follow-up and an increase in PD were observed. For low doses (less than 30 Gy) PD and cMy returned to baseline (=pre-operative status), while for high doses (>30 Gy) the change increased during the full extent of the follow-up period. No difference could be established for R1. For R2 an increase was observed during the first year, which then gradually returned to baseline. For R2, stronger effects were seen as a consequence of higher absorbed doses. Conclusion: In the long-term follow-up for glioma patients, qMRI is a powerful tool for detecting small changes, such as a decrease of myelin concentration, in NAWM after CRT.

Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms.

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC. DESIGN: Women with IBS (n = 75), MDD (n = 41) and their respective HC (n = 39 and n = 43) underwent structural brain MRI. IC subregion volumes were estimated using statistical parametric mapping software. General linear model approaches were applied to IC volumetric data and FDR-corrected partial correlation analyses assessed relations between GMV, GI symptoms and Glx concentrations. RESULTS: IBS patients had significantly smaller IC subregions than HC in both hemispheres but there was no significant difference between MDD compared with IBS and HC for any insular subregion. In IBS, the dorsal anterior insular volumes were negatively correlated with symptoms of nausea and pain, and the left ventral subregion showed a positive correlation with straining to defecate, while the posterior subregion volumes showed no relation to symptoms. In the anterior insula, concentration of Glx showed positive correlations with GMV bilaterally in HC and with GMV of the right anterior insula in IBS. CONCLUSION: As the interoceptive cortex, the insula shows substantial and disease-specific structural differences in patients with chronic interoceptive visceral pain. Particularly changes in the anterior proportions might be related to chronic exposure to or enhanced salience towards adverse interoceptive visceral signals and could be linked to biochemical changes, calling for further multimodal and longitudinal work.

MRI of nigrosome-1: A potential triage tool for patients with suspected parkinsonism.

BACKGROUND AND PURPOSE: Susceptibility-weighted imaging (SWI) of nigrosome-1 is an emerging and clinically applicable imaging marker for parkinsonism, which can be derived from routinely performed brain MRI. The purpose of the study was to assess whether SWI can be used as a triage tool for more efficient selection of subsequent Dopamine Transporter Scan (DaTSCAN) single-photon emission computed tomography (SPECT). METHODS: We examined 72 consecutive patients with suspected parkinsonism with both DaTSCAN SPECT and SWI (48 in Philips Ingenia, 24 in GE Signa). Additionally, we examined 24 healthy controls with SWI (14 in Philips Ingenia, 10 in GE Signa). Diagnostic performance of SWI and DaTSCAN SPECT was assessed on the basis of clinical diagnosis, in terms of sensitivity, specificity, and diagnostic accuracy. RESULTS: A total of 54 parkinsonism patients (69 years ± 9, 32 men), 18 nonparkinsonism patients (69.4 years ± 9, 10 men), and 24 healthy controls (62 years ± 8, 10 men) were recruited. SWI had a specificity of 92% and a sensitivity of 74%, whereas DaTSCAN SPECT had 83% and 94%, respectively. By preselecting patients with abnormal or inconclusive SWI, the diagnostic performance of DaTSCAN SPECT improved (specificity 100%, sensitivity 95%). Scans from Philips were associated with significantly lower image quality compared to GE (p < .001). The experienced rater outperformed the less experienced one in diagnostic accuracy (82% vs. 68%). CONCLUSIONS: SWI can be used as triage tool because normal SWI can in most cases rule out parkinsonism. However, the performance of SWI depends on acquisition parameters and rater's experience.

Magnetic resonance imaging incidents are severely underreported: a finding in a multicentre interview survey.

OBJECTIVES: The purpose of this study was to develop a procedure to investigate the occurrence, character and causes of magnetic resonance (MR) imaging incidents. METHODS: A semi-structured questionnaire was developed containing details such as safety zones, examination complexity, staff MR knowledge, staff categories, and implementation of EU directive 2013/35. We focused on formally reported incidents that had occurred during 2014-2019, and unreported incidents during one year. Thirteen clinical MR units were visited, and the managing radiographer was interviewed. Open questions were analysed using conventionally adopted content analysis. RESULTS: Thirty-seven written reports for 5 years and an additional 12 oral reports for 1 year were analysed. Only 38% of the incidents were reported formally. Some of these incidents were catastrophic. Negative correlations were observed between the number of annual incidents (per scanner) and staff MR knowledge (Spearman's rho - 0.41, p < 0.05) as well as the number of MR physicists per scanner (- 0.48, p < 0.05). It was notable that only half of the sites had implemented the EU directive. Quotes like 'Burns are to be expected in MR' and not even knowing the name of the incident reporting system suggested an inadequate safety culture. Finally, there was a desire among staff for MR safety education. CONCLUSIONS: MR-related incidents were greatly underreported, and some incidents could have had catastrophic outcomes. There is a great desire among radiographers to enhance the safety culture, but to achieve this, much more accessible education is required, as well as focused involvement of the management of the operations. KEY POINTS: • Only one in three magnetic resonance-related incidents were reported. • Several magnetic resonance incidents could have led to catastrophic consequences. • Much increased knowledge about magnetic resonance safety is needed by radiologists and radiographers.

Publisher Correction: Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Imaging Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity.

OBJECTIVE: Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients. METHODS: Ten essential tremor patients (prior to deep brain stimulation surgery) and six healthy controls, were scanned using a 3 T MR system. GABA+ and Glx concentrations were measured using magnetic resonance spectroscopy (MRS) performed using single voxel MEGA-PRESS. For the purpose of assessing the tremor severity, the essential tremor rating scale (ETRS) was used in accordance with Fahn, Tolosa, and Marin. RESULTS: We demonstrated that the cerebellar GABA+/Glx ratio was positively correlated to the ETRS (r = 0.70, p = 0.03) in essential tremor. Cerebellar and thalamic GABA+ and Glx concentrations did not show any significant difference when comparing essential tremor patients with healthy controls, at the group level. CONCLUSION: We demonstrated a positive correlation between increasing tremor disability and the ratio of GABA+/ Glx in the cerebellum of essential tremor patients. This highlights the impact of an altered balance of the excitatory and inhibitory neurotransmitters in tremor severity. Rather than a change in GABA+, which was constant, we attribute this finding to an overall decrease of Glx.

Retinal thinning and brain atrophy in early MS and CIS.

BACKGROUND: Optical coherence tomography (OCT) could be complementary to magnetic resonance imaging (MRI) of the brain in monitoring course of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Thinning of neurons in ganglion cell-inner plexiform layer (GCIPL) measured by OCT is assumed to be associated with brain atrophy. OBJECTIVES: To evaluate association of GCIPL with brain parameters detected by quantitative MRI (qMRI) and MR-spectroscopy (MRS) in early MS and CIS. METHODS: Seventeen newly diagnosed MS and 18 CIS patients were prospectively included. The patients were assessed at baseline as well as at 1 year follow-up by OCT, qMRI and MRS. Brain parenchymal and myelin volumes (BPV, MYV respectively) and the corresponding fractions (BPF, MYF) were measured with qMRI. Metabolites including myo-inositol (myo-Ins) were measured in the normal-appearing white matter (NAWM) using MRS. T-tests and ANOVA were used to analyze group differences, and linear regression models to evaluate association of GCIPL with BPV, MYV and myo-Ins after correlation analysis. RESULTS: Disease activity reflected by lesions on MRI and presence of CSF oligoclonal IgG bands were more prominent in MS compared to CIS. GCIPL, BPV, MYV, BPF and MYF were reduced, while concentration of myo-Ins was increased in MS compared to CIS. Follow-up showed consistency of thinner GCIPL in MS compared to CIS. GCIPL thinning correlated with reduced BPV and MYV (P < .05 for both), but with increased myo-Ins (P < .01). CONCLUSIONS: Significant GCIPL thinning occurs in early MS and is associated with enhanced brain inflammation and atrophy.

Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Tensor Imaging Study.

Idiopathic normal pressure hydrocephalus (iNPH) is a disorder with unclear pathophysiology. The diagnosis of iNPH is challenging due to its radiological similarity with other neurodegenerative diseases and ischemic subcortical white matter changes. By using Diffusion Tensor Imaging (DTI) we explored differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in iNPH patients (before and after a shunt surgery) and healthy individuals (HI) and we correlated the clinical results with DTI parameters. Thirteen consecutive iNPH-patients underwent a pre- and post-operative clinical work-up: 10 m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs); for cognitive function MMSE. Nine HI were included. DTI was performed before and 3 months after surgery, HI underwent DTI once. DTI differences analyzed by manually placing 12 regions-of-interest. In patients motor and balance function improved significantly after surgery (p = 0.01, p = 0.025). Higher nearly significant FA values found in the patients vs HI pre-operatively in the thalamus (p = 0.07) accompanied by an almost significant lower ADC (p = 0.08). Significantly FA and ADC-values were found between patients and HI in FWM (p = 0.02, p = 0.001) and almost significant (p = 0.057) pre- vs postoperatively. Postoperatively we found a trend towards the HIs FA values and a strong significant negative correlation between FA changes vs. gait results in the FWM (r = -0.7, p = 0.008). Our study gives a clear indication of an ongoing pathological process in the periventricular white matter, especially in the thalamus and in the frontal white matter supporting the hypothesis of a shunt reversible thalamo-cortical circuit dysfunction in iNPH.

Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome.

Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.

Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstrate altered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However, alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changes remain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthy controls [HC]) with respect to aINS glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations and addressed possible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonance spectroscopy of bilateral aINS to assess Glx and GABA+ concentrations. Questionnaire data from all participants and prospective symptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related and psychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P < 0.05, right aINS P < 0.001), whereas no group differences were detected for GABA+ concentrations. Lower right-lateralized Glx concentrations in patients were substantially predicted by longer pain duration, while less frequent use of adaptive pain-coping predicted lower Glx in left aINS. Our findings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results also indicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and of the left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

Retrospective artifact elimination in MEGA-PRESS using a correlation approach.

PURPOSE: To develop a method for retrospective artifact elimination of MRS data. This retrospective method was based on an approach that combines jackknife analyses with the correlation of spectral windows, and therefore termed "JKC." METHODS: Twelve healthy volunteers performed 3 separate measurement protocols using a 3T MR system. One protocol consisted of 2 cerebellar MEGA-PRESS measurements: 1 reference and 1 measurement including head movements. One-third of the artifact-influenced datasets were treated as training data for the implementation the JKC method, and the rest were used for validation. RESULTS: The implemented JKC method correctly characterized most of the validation data. Additionally, after elimination of the detected artifacts, the resulting concentrations were much closer to those computed for the reference datasets. Moreover, when the JKC method was applied to the reference data, the estimated concentrations were not affected, compared with standard averaging. CONCLUSION: The implemented JKC method can be applied without any extra cost to MRS data, regardless of whether the dataset has been contaminated by artifacts. Furthermore, the results indicate that the JKC method could be used as a quality control of a dataset, or as an indication of whether a shift in voxel placement has occurred during the measurement.

Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis.

BACKGROUND: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. METHODS: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. "No evidence of disease activity-3" (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI®) were recorded during 4 years of follow-up. RESULTS: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p < 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. CONCLUSIONS: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.

How does motion affect GABA-measurements? Order statistic filtering compared to conventional analysis of MEGA-PRESS MRS.

PURPOSE: The aim of this study was to evaluate two post-processing techniques applied to MRS MEGA-PRESS data influenced by motion-induced artifacts. In contrast to the conventional averaging technique, order statistic filtering (OSF) is a known method for artifact reduction. Therefore, this method may be suitable to incorporate in the GABA quantification. METHODS: Twelve healthy volunteers were scanned three times using a 3 T MR system. One measurement protocol consisted of two MEGA-PRESS measurements, one reference measurement and one measurement including head motions. The resulting datasets were analyzed with the standard averaging technique and with the OSF-technique in two schemes; filtering phase cycles 'RAW PC' and filtering dynamics 'RAW Dyn'. RESULTS: The datasets containing artifacts resulted in an underestimation of the concentrations. There was a trend for the OSF-technique to compensate for this reduction when quantifying SNR-intense signals. However, there was no indication that OSF improved the estimated GABA concentrations. Moreover, when only considering the reference measurements, the OSF technique was equally as effective as averaging, which suggests that the techniques are interchangeable. CONCLUSION: OSF performed equally well as the conventional averaging technique for low-SNR signals. For high-SNR signals, OSF performed better and thus could be considered for routine usage.

Quantitative MRI for analysis of peritumoral edema in malignant gliomas.

BACKGROUND AND PURPOSE: Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R1, transverse relaxation R2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. METHODS: In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R1, R2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. RESULTS: R1, R2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (P < .0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. CONCLUSION: Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R1 and R2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI.

The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and edema in the brain. The model relates simultaneous measurement of R1 and R2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume, and excess parenchymal water partial volume. The model parameters were obtained using spatially normalized brain images of a group of 20 healthy controls. The pathological brain was modeled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of edema. The method was tested on spatially normalized brain images of a group of 20 age-matched multiple sclerosis (MS) patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL), a 38 mL smaller myelin volume (119 vs. 157 mL), and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL). Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6 ± 1.5% lower for gray matter (GM) structures and 2.8 ± 1.0% lower for white matter (WM) structures. The excess parenchymal water partial volume was 9 ± 10% larger for GM and 5 ± 2% larger for WM. Manually placed ROIs indicated that the results using the template ROIs may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects: a 45-year-old healthy subject, a 72-year-old healthy subject, and a 45-year-old MS patient. The observed results agreed with the expected behavior considering both age and disease. In conclusion, the proposed model may provide clinically important parameters, such as the total brain volume, degree of myelination, and degree of edema, based on a single qMRI acquisition with a clinically acceptable scan time.

Multi-parametric representation of voxel-based quantitative magnetic resonance imaging.

The aim of the study was to explore the possibilities of multi-parametric representations of voxel-wise quantitative MRI data to objectively discriminate pathological cerebral tissue in patients with brain disorders. For this purpose, we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19 age and gender matched healthy subjects as a reference group. The subjects were examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue structure parameters: relaxation rates, R(1) and R(2), and proton density. The resulting parameter images were normalized to a standard template. Tissue structure in MS patients was assessed by voxel-wise comparisons with the reference group and with correlation to a clinical measure, the Expanded Disability Status Scale (EDSS). The results were visualized by conventional geometric representations and also by multi-parametric representations. Data showed that MS patients had lower R(1) and R(2), and higher proton density in periventricular white matter and in wide-spread areas encompassing central and sub-cortical white matter structures. MS-related tissue abnormality was highlighted in posterior white matter whereas EDSS correlation appeared especially in the frontal cortex. The multi-parameter representation highlighted disease-specific features. In conclusion, the proposed method has the potential to visualize both high-probability focal anomalies and diffuse tissue changes. Results from voxel-based statistical analysis, as exemplified in the present work, may guide radiologists where in the image to inspect for signs of disease. Future clinical studies must validate the usability of the method in clinical practice.

Normal appearing and diffusely abnormal white matter in patients with multiple sclerosis assessed with quantitative MR.

INTRODUCTION: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both 'normal appearing white matter' (NAWM) and 'diffusely abnormal white matter' (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes. In this study, qMRI and qMRS were used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to 'normal white matter' (NWM) in healthy controls. METHODS: QMRI and qMRS measurements were performed on a 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the 'Barkhof-Tintoré criteria' for MS, ('MRIpos'), whereas 15 showed radiologically atypical findings with few WM lesions ('MRIneg'). QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS. RESULTS: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. CONCLUSIONS: Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox.