Quantitative Susceptibility Mapping Research Articles

Quantification of the Brain Iron Metabolism in the Cognitively Declined Adults Using 7T MRI

AbstractBackgroundThe extracellular aggregation of beta‐amyloid (AB) plaques is one of the hallmark pathology of Alzheimer’s diseases (AD) that develops years prior to clinical symptoms. However, inconsistency in the rate of cognitive decline among subjects with AB pathology and ineffectiveness of anti‐amyloid therapeutics to mitigate cognitive impairment suggest that other parameters, such as patterns of brain iron, may impact the risk of cognitive decline. In this study we leveraged improved MRI signal at 7T to explore susceptibility changes in the iron‐enriched regions among individuals with AD/MCI and healthy controls (HCs) through quantitative susceptibility mapping (QSM) with unprecedented resolution.MethodIn vivo MRI experiment was performed in AD/MCI and age‐matched healthy subjects. Scanning was conducted on a 7T MRI scanner using 1Tx/32Rx Nova head coil. To calculate QSM, a 3D high‐resolution spoiled gradient echo (GRE) sequence was used (voxels size = 0.3×0.3×1.5 mm3). QSM was used to measure susceptibility in the major iron‐enriched structures (Fig. 1), including red nucleus (RN), substantia nigra (SN), globus pallidus (GP), Caudate nucleolus (CN), putamen (PT), and dentate nucleus (DN).ResultWe found a significantly higher magnetic susceptibility in GP and DN in patients with AD/MCI compared with HCs (Fig. 2). Overall mean susceptibility values for the RN, SN, CN, GP, PT, and DN in AD/MCI and HCs is summarized in Table 1. In AD/MCI the highest susceptibility values were found in the GP (233.5±12.7) and DN (214.7±10.4), verses 174.6±11.8 and 168.9±11.6 for GP and DN in the HCs, respectively. There were small differences in the susceptibility values between the other ROIs.ConclusionWe reported an initial result for QSM at 7T in the AD/MCI subjects and appropriate age matched HCs. The main aim of the study was to investigate whether susceptibility values measured using ultra‐high resolution QSM differ in the iron‐enriched regions between these two populations. A significant susceptibility value was reported in the AD/MCI compared with the HC in GP and DN regions. This observation clearly deserves further investigations in larger cohorts.

MRI Markers for Detecting Accelerated Alzheimer’s Disease after Neurotrauma

AbstractBackgroundA history of traumatic brain injury (TBI) is linked to an earlier onset of Alzheimer’s disease (AD) (Nemetz et al., 1999). Evidence showed that the more severe the injury, the greater risk of developing AD (Johnson et al.,2010). However, systematic evaluation of in vivo MRI markers in the monitoring of AD progression after trauma is lacking. Here, we investigated the performance of various MRI markers in tracking AD progression after neurotrauma in a mouse model of AD. The following MRI sequences were investigated: dynamic contrast‐enhanced (DCE) MRI, Fluid attenuated inversion recovery (FLAIR) MRI, Quantitative Susceptibility Mapping (QSM) and diffusion MRI.Method3xTg‐AD mice (Jackson Laboratory, ME) were bred and maintained at Boston University. Unanesthetized mice were pretreated with a non‐sedating dose of the analgesic buprenorphine (0.2mg/kg, i.p.) prior to TBI. Male and female 3xTg‐AD mice were subjected to left‐lateral closed‐head impact injury at 10‐12 weeks of age as described in our previous work (Tagge et al., 2018). MRI data were acquired at 1 day, 3 days, 1 month and 3 months post TBI. DCE‐MRI was analyzed using in‐house software programmed in Matlab (Mathworks, MA). The volume of white matter hyperintensity was measured using manual contours in ImageJ (NIH). QSM data was analyzed using JHU/KKI QSM Toolbox (Li et al, 2019). Diffusion MRS was analyzed in DSI Studio (http://dsistudio.labsolver.org). Age, gender matched 3xTg‐AD mice without TBI were used as controls.ResultIncreased blood‐brain permeability was detected by DCE‐MRI and changes of white matter susceptibility detected by QSM were observed in the subacute phase (1‐3 days) post TBI. Accelerated development of white matter hyperintensity was observed as early as 1 month post TBI.ConclusionMRI markers provide valuable measures of the integrities of blood‐brain barrier and white matter after neurotrauma in vivo, and have the potential to facilitate the management of neurotrauma subjects with a risk of accelerated AD development.

Histogram analysis of quantitative susceptibility mapping and apparent diffusion coefficient for identifying isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

Accurate preoperative identification of isocitrate dehydrogenase (IDH) genotypes and tumor subtypes is highly important for proper treatment planning and prognosis evaluation in patients with glioma. This study aimed to differentiate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using histogram features of quantitative susceptibility mapping (QSM) and apparent diffusion coefficient (ADC). This prospective study enrolled patients with suspected gliomas between March 2019 and January 2022 in a random series. Histogram features of QSM and ADC were extracted from the tumor parenchyma. The Mann-Whitney U test was used to compare the difference in histogram features between different IDH genotypes and among tumor subtypes. Receiver operating characteristic (ROC) curves were constructed to assess the corresponding diagnostic performance. This study included 47 patients with histopathologically confirmed adult-type diffuse gliomas. Totals of seven QSM features including 10th percentile (P10), 90th percentile (P90), interquartile range (IQR), maximum, mean absolute deviation (MAD), root mean squared (RMS), and variance, and five ADC features including P10, mean, median, RMS, and skewness exhibited significant differences between different IDH genotypes (P<0.05 for all), with the IQR of QSM demonstrating the highest area under curve (AUC) of 0.774 [95% confidence interval (CI): 0.635-0.913]. For separating tumor subtypes, the IQR of QSM also showed the highest AUC of 0.745 (95% CI: 0.566-0.924) for glioblastoma (GBM) versus astrocytoma and 0.848 (95% CI: 0.706-0.989) for GBM versus oligodendroglioma, but none of the features could discriminate astrocytoma from oligodendroglioma. The combination of the IQR of QSM, P10 of ADC, and age achieved the highest AUC of 0.910 (95% CI: 0.826-0.994) for IDH genotypes, and 0.939 (95% CI: 0.859-1.000) and 0.967 (95% CI: 0.904-1.000) for GBM versus astrocytoma and GBM versus oligodendroglioma, respectively. QSM and ADC histogram features may serve as potential imaging markers for noninvasively assessing IDH genotypes and tumor subtypes of adult-type diffuse gliomas. Combining significant features may enhance the diagnostic performance substantially.

Correlation of brain iron deposition and freezing of gait in Parkinson's disease: a cross-sectional study.

Quantitative susceptibility mapping (QSM) is a novel imaging method for detecting iron content in the brain. The study aimed determine whether the iron deposition in the brains of people with Parkinson's disease (PD) is correlated with freezing of gait (FOG). We retrospectively collected the data of 24 patients with PD from the Movement Disorders Program and 36 healthy controls (HCs) from January 2021 to December 2021. Clinical assessments included mental intelligence scales, Parkinson rating scales, motor-related scales, and clinical gait assessments. All exercise scales and gait assessments were performed in the "ON" and "OFF" states. Magnetic resonance imaging (MRI) data were collected using 3-dimensional fast low-angle shot sequences. We chose the bilateral red nucleus, substantia nigra, thalamus, putamen, caudate nucleus, and globus pallidus as regions of interest for QSM analysis. The iron deposition in the substantia nigra of the PD group was significantly higher than that of the HC group (P<0.01). In the PD group, the iron deposition in the substantia nigra of patients with FOG was significantly higher than that in patients without FOG (P=0.04). The iron deposition in the substantia nigra was positively correlated with the New Freezing of Gait Questionnaire (P=0.03). The scores for depression and anxiety of the PD group were significantly higher than those of the HC group, while the Berg balance scale score was significantly lower (P<0.01). The iron deposition in the substantia nigra of patients with PD is increased compared with that of controls and is associated with FOG. QSM can be used to detect brain iron deposition in patients with PD, which would help to explore the mechanism of abnormal neurobiological activity in FOG.

Baseline cerebrovascular reactivity predicts longitudinal enlarged perivascular space burden in the basal ganglia among cognitively normal older adults

AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development.Method79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS).ResultBGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = &lt;0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = &lt;0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = &lt;0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449).ConclusionThese results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction.

Using 7T MRI to study hippocampal structures in Alzheimer’s disease and post‐SARS‐CoV2 infection

AbstractBackground7T MRI allows implementation of high‐resolution quantitative susceptibility mapping (QSM) which can be used to assess the cerebral microvascular/hypoperfusion pathogenic hypothesis in Alzheimer’s disease (AD) and in the post‐SARS‐CoV2 setting to explore if there may be similarities in brain changes in these two conditions. The magnetic susceptibility (reflective of tissue iron) of hippocampal subfields was assessed in patients with 1) CSF‐Amyloidß‐status AD; 2) mild COVID‐19 over 6 months previously (Cv); 3) severe COVID‐19 with ICU admission &gt;6 months previously (ICU‐Cv); and 4) age‐matched healthy controls (HC).Methods33 participants (10 HC, 14 Cv, 9 ICU‐Cv) for the COVID study and 24 participants (14 AD, 11HC) from AD patients with confirmed CSF‐Amyloidß levels, aged 42‐79, were scanned on a 7T scanner with the following protocol T2* GRE for the AD groups (0.7×0.7×0.7mm3,TE/TR = 20/31ms) and T2* multi‐echo GRE for the Cv groups (0.38×0.38×0.75mm3,TE1/TE2/TR = 8.2/18.4/24ms). Data were processed using QSMbox1 to produce susceptibility maps. PSIR (0.55×0.55×0.55mm3,TE/TR = 3.1/6.9ms) and T2‐weighted FSE (0.38×0.39×1.5mm3, TE/TR = 117/5900ms) images were used to segment the hippocampal subfields (Figure 1)2. One‐way analyses were used in SPSS for comparison between the HC group and each of the Cv, ICU‐Cv, and AD groups.ResultsThere was no change in susceptibility for the whole hippocampus between AD and HC, but there was a significant difference for the DG subfield (p = 0.045), Figure 2. For COVID patients, there was a significant difference between the susceptibility of the whole hippocampus in the ICU‐Cv group (p = 0.035), but not in the Cv group (p = 0.788), Figure 3, compared to HC. In subfield analyses there was a trend towards decreased susceptibility in the subiculum, an area known to be affected by Alzheimer pathology, in the ICU‐Cv group (p = 0.032) compared to HC.ConclusionThe lower susceptibility within the hippocampal structures observed in AD and ICU‐Cv patients may reflect less iron either from cerebral hypoperfusion or vascular injuries in AD or additionally result from sequelae of hypoxaemia in ICU‐Cv. The study provides preliminary evidence of detectable in vivo microstructural changes in hippocampal subfields in both AD and post‐COVID settings. Funding: Medical Research Council, UK (MR/T005580/1); National Institute of Health, USA (1R56AG074467‐01)

A Causality-Driven Graph Convolutional Network for Postural Abnormality Diagnosis in Parkinsonians.

Abnormal posture is a common movement disorder in the progress of Parkinson's disease (PD), and this abnormality can increase the risk of falls or even disabilities. The conventional assessment approach depends on the judgment of well-trained experts via canonical scales. However, this approach requires extensive clinical expertise and is highly subjective. Considering the potential of quantitative susceptibility mapping (QSM) in PD diagnosis, this study explored the QSM-based method for the automated classification between PD patients with and without postural abnormalities. Nevertheless, a major challenge is that unstable non-causal features typically lead to less reliable performance. Therefore, we propose a causality-driven graph-convolutional-network framework based on multi-instance learning, where performance stability is enhanced through the invariant prediction principle and causal interventions. Specifically, we adopt an intervention strategy that combines a non-causal intervenor with causal prediction. A stability constraint is proposed to ensure robust integrated prediction under different interventions. Moreover, an intra-class homogeneity constraint is enforced for each individually-learned causality scoring module to promote the extraction of group-level general features, and hence achieve a balance between subject-specific and group-level features. The proposed method demonstrated promising performance through extensive experiments on a real clinical dataset. Also, the features extracted by our method coincide with those reported in previous medical studies on PD posture abnormalities. In general, our work provides a clinically-valuable approach for automated, objective, and reliable diagnosis of postural abnormalities in Parkinsonians. Our source code is publicly available at https://github.com/SJTUBME-QianLab/CausalGCN-PDPA.

Healthy Dietary Intake Reduces Longitudinal Brain Iron Accumulation in Older Adults

AbstractBackgroundBrain iron, which tends to accumulate with normal aging, negatively affects cognitive performance. However, the impact of brain iron on cognition appears modifiable. In a recent study from our group [1], we demonstrated that those older adults with high dietary intake of antioxidants, iron chelating nutrients and polyunsaturated fatty acids (Factor 2 in [1]), tended to have lower brain iron and better working memory performance than expected for their age. Here, we extend our previous work by evaluating associations between baseline consumption of Factor 2 nutrients and longitudinal brain iron accumulation, evaluated three years after baseline.MethodsForty‐three, cognitively normal, older adults (26 women, age range 63‐88 years) underwent MRI‐based structural brain imaging and quantitative susceptibility mapping for assessment of brain iron concentration at two time points: baseline (T1) and three years after baseline (T2). Additionally, at T1, nutritional‐intake was assessed via a validated questionnaire. Nutrients were grouped into nutrition factors based on previous literature and factor analysis. Factor 2, comprised vitamin E, lysine, DHA omega‐3 and LA omega‐6, representing antioxidants, iron chelating nutrients and polyunsaturated fatty acids.ResultsVoxelwise, whole‐brain, linear mixed‐effects models (qFDR &lt; 0.05), controlling for longitudinal gray matter volume alterations, age, gender and education, revealed brain iron accumulation within several subcortical and cortical brain regions. Importantly, a significant time point by nutrition interaction was also observed. Specifically, those participants who consumed higher amounts of Factor 2 nutrients at baseline exhibited lower longitudinal brain iron accumulation within the left middle frontal gyrus, left superior parietal lobule, left insular cortex, right inferior temporal cortex, and bilateral hippocampus. Time point by nutrition interactions were not observed for other nutrition factors discussed in [1], such as those comprised of nutrients found in fruits and vegetables, or in green tea.ConclusionOur results indicate that dietary patterns rich in oxidative stress‐reducing antioxidants, iron chelating nutrients and polyunsaturated fatty acids may slow down age‐related, brain iron accumulation in older adults.

Lifestyle, biological and genetic determinants of brain iron accumulation in aging

AbstractBackgroundOptimal iron levels are crucial for brain cells’ functioning. However, brain iron overload occurs in both normal aging and neurodegenerative disorders, including Alzheimer’s disease (AD). High iron concentration triggers oxidative stress and neuroinflammation, both involved the AD pathophysiology. Despite growing evidence of the toxicity of iron overload, why iron accumulates remains unknown. A few studies have linked higher brain iron content to alcohol use, body mass index, cardiovascular health, and smoking. However, no study has investigated the factors behind iron accumulation longitudinally.MethodWe investigated the associations between potential determinants such as blood markers of iron metabolism, cardiovascular health (Framingham’s risk score; FRS), lifestyle factors (smoking, alcohol use, physical activity), ApoE (any e4) status, and iron content and iron accumulation using longitudinal data (n = 208 healthy volunteers, age = 20‐79, mean follow‐up time = 2.75 years) from the IronAge study. Iron was assessed with Magnetic Resonance Imaging using quantitative susceptibility mapping for iron‐rich or age‐sensitive regions (caudate (CA), putamen (PU), pallidum (PA), dorsolateral prefrontal cortex (DLPFC)). We used structural equation modelling to assess the relationships between determinants and iron accumulation.ResultHigher blood ferritin was related to higher iron content and iron accumulation in DLPFC (B = 0.181 and 0.173), CA (B = 0.158 and 0.225) and PU (B = 0.127 and 0.263). Higher blood haemoglobin was related to higher iron content in DLPFC (β = 0.177) and CA (β = 0.178), as well as to iron accumulation in PA (β = 0.220). Higher blood transferrin was related to lower iron content and iron accumulation in CA (B = ‐0.131 and ‐0.147) and PU (B = ‐0.160 and ‐0.232). Lower FRS was related to greater iron accumulation in DLPFC among younger adults (β = ‐0.379, age&lt;40). Increased FRS was related to greater iron accumulation (β = 0.194). More physical activity was related to higher iron content in PA among younger adults (β = 0.231, age&lt;40). Lastly, older (age&gt;40) ApoE e4 carriers had higher iron content in PA (β = 0.219). No associations were found with alcohol or smoking. These results were independent of, sex, education, atrophy, white‐matter lesions, and age unless age‐stratified results.ConclusionOur study identified modifiable and non‐modifiable factors of brain iron accumulation in adulthood. The former can be targeted to prevent accelerated iron accumulation.

Epiphyseal cartilage vascular architecture at the distal humeral osteochondritis dissecans predilection site in juvenile pigs.

Failure of endochondral ossification due to interruption of the vascular supply to the epiphyseal cartilage is a critical step in the development of osteochondritis dissecans (OCD). Herein we describe the vascular architecture of the distal humeral epiphyseal cartilage in pigs and identify characteristic features that have been associated with sites predisposed to OCD development across species. Distal humeral specimens were harvested from pigs (n = 5, ages = 1, 10, 18, 30, and, 42 days old) and imaged at 9.4T magnetic resonance imaging (MRI) using a 3D gradient recalled echo sequence. The MRI data were processed using a quantitative susceptibility mapping (QSM) pipeline to visualize the vascular architecture. Specimens were also evaluated histologically to identify the presence of ischemic epiphyseal cartilage necrosis (osteochondrosis [OC]-latens) and associated failure of endochondral ossification (OC-manifesta). The QSM data enabled visualization of two distinct vascular beds arising from the perichondrium at the lateral and medial aspects of the distal humeral epiphysis. Elongated vessels originating from these beds coursed axially to supply the lateral and medial thirds of epiphyseal cartilage. At 18 days of age and older, a shift from perichondrial to transosseous blood supply was noted axially, which appeared more pronounced on the lateral side. This shift coincided with histologic identification of OC-latens (30- and 42-day-old specimens) and OC-manifesta (18- and 42-day-old specimens) lesions in the corresponding regions. The vascular anatomy and its evolution at the distal humeral epiphysis closely resembles that previously reported at predilection sites of knee OCD, suggesting a shared pathophysiology between the knee and elbow joints.

Prospective MRI and Neurocognitive Assessment of “Chemobrain” in Acute Myeloid Leukaemia: The Mineral Study

CONCLUSIONS “Chemobrain” is commonly reported by patients treated for Acute Myeloid Leukaemia (AML), potentially attributable to chemotherapy or iron overload. We aimed to determine whether “chemobrain” could be objectively detected in AML patients. We performed a prospective, observational, longitudinal cohort study in adults commencing chemotherapy for AML, powered to capture a potential 25% incidence of “chemobrain.” Participants underwent neurocognitive assessment (NCA) and brain magnetic resonance imaging (MRI), including iron quantitative susceptibility mapping (QSM), as a biomarker of neuro-inflammation, at three timepoints: pre-treatment (T1), end of treatment (T2), and 6 months later (T3). Longitudinal changes of minimum 1.64 SD were considered significant. The primary outcome was change in NCA score between T1-T2, with secondary correlation analyses between NCA, MRI, QSM and clinical data. This study was funded by a RBWH Foundation 2018 Diamond Care Grant. Between January 2019 and June 2021, 20 patients were enrolled; of these, 15 and 10 remained alive/enrolled for evaluation at T2 and T3 respectively. Overall NCA scores for the cohort between T1-T2 were similar; however, four (27%) participants performed significantly worse (-1.64SD) in Language or Verbal Memory, with three returning to baseline at T3. Objective NCA score did not correlate with subjective symptoms, and quality of life and physical fatigue improved T1-T2. Cohort brain volumes were similar T1-T2; however, correlation analysis identified interesting potential associations between worse Language performance and volume loss in grey matter (GM; p=0.021) and Wernicke's area (p=0.02), and suggested increased iron susceptibility in frontal lobe (p=0.041) and possibly cortical GM (p=0.055). Despite patient-reported symptoms, objective neurological toxicity appears uncommon in AML patients, and those with measurable impairment appear to subsequently return to baseline.

Quantitative iron–neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification

BackgroundNeuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case–control PD cohort, we evaluated the diagnostic accuracy of quantitative iron–neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association.MethodsPD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin–iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity.ResultsIn total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p &amp;lt; 0.0001) and smaller sizes after thresholding for low susceptibility (p &amp;lt; 0.0001) on QSM and (b) lower contrast range (p &amp;lt; 0.0001) and smaller sizes after thresholding for high-signal voxels (p &amp;lt; 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4&amp;lt; | r | &amp;lt;0.6, p &amp;lt; 0.0001), respectively. A composite quantitative neuromelanin–iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI.ConclusionQuantitative neuromelanin–iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.

Toward a deep learning-based magnetic resonance imaging only workflow for postimplant dosimetry in I-125 seed brachytherapy for prostate cancer

Background and purposeThe current standard imaging-technique for creating postplans in seed prostate brachytherapy is computed tomography (CT), that is associated with additional radiation exposure and poor soft tissue contrast. To establish a magnetic resonance imaging (MRI) only workflow combining improved tissue contrast and high seed detectability, a deep learning-approach for automatic seed segmentation on MRI-scans was developed. Material and methodsPatients treated with I-125 seed brachytherapy received a postplan-CT and a 1.5 T MRI-scan on nominal day 30 after implantation. For MRI-based seed visualization, DIXON-sequences were acquired and deep learning-based quantitative susceptibility maps (QSM) were generated from 3D-gradient-echo-sequences from 20 patients. Seed segmentations created on CT served as ground truth. For automatic seed segmentation on MRI, a 3D nnU-net model was trained using QSM and DIXON, both solely and combined. ResultsOf the implanted seeds 94.8 ± 2.4% were detected with deep learning automatic segmentation entrained on both QSM and DIXON data. Models trained on the individual sequence data-sets performed worse with detection rates of 87.5 ± 2.6% or 88.6 ± 7.5% for QSM and DIXON respectively. The seed centers identified on CT versus QSM and DIXON were on average 1.8 ± 1.3 mm apart. Postimplant dosimetry for evaluation of positioning inaccuracies revealed only small variations of up to 0.4 ± 4.26 Gy in D90 (dose 90% of the prostate receives) between the standard CT-approach and our MRI-only workflow. ConclusionThe proposed deep learning-based MRI-only workflow provided a promisingly accurate and robust seed localization and thus has the potential to compete with current state-of-the-art CT-based postimplant dosimetry in the future.

Altered brain iron deposition in patients with minimal hepatic encephalopathy: an MRI quantitative susceptibility mapping study

To explore the use of quantitative susceptibility mapping (QSM) in assessing changes in brain iron deposits and their association with cognitive function in patients with minimal hepatic encephalopathy (MHE). The study cohort comprised 27 cases with hepatitis B-associated cirrhosis with MHE (MHE group), 25 with hepatitis B-associated cirrhosis without MHE (NMHE group), and 25 healthy controls (HC group). Iron deposits in the bilateral frontal white matter, caudate nucleus (CN), putamen, globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus, and dentate nucleus were measured by QSM. The associations between iron deposition with the time taken to complete number connection tests A (NCT-A) and the score on digital-symbol test (DST) were analysed. Susceptibility values differed significantly in the bilateral CN, left thalamus, right SN, and left hippocampus in the MHE group compared with the other groups and were positively associated with the times taken to complete the NCT-A in the bilateral CN, left thalamus, and right SN and negatively associated with DST scores in the bilateral CN, left TH, and left HP. Reduced cognitive function in MHE patients was significantly associated with abnormally increased iron deposition in certain brain areas. The quantification of brain iron deposition by QSM may thus be an objective and accurate means of evaluating MHE.

Changes in brain susceptibility in Wilson’s disease patients: a quantitative susceptibility mapping study

To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.

Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.

Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.

Microstructural and functional alterations of the ventral pallidum are associated with levodopa-induced dyskinesia in Parkinson's disease.

The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa-induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD-LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). Thirty-one PD-LID patients, 39 PD patients without LID (PD-nLID), and 28 healthy controls (HCs) underwent T1-weighted MRI, quantitative susceptibility mapping, multi-shell diffusion MRI, and resting-state functional MRI (rs-fMRI). Different measures characterizing the VP were obtained using a region-of-interest-based approach. The left VP in the PD-LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD-nLID and HC groups. Rs-MRI revealed that, compared with the PD-nLID group, the PD-LID group in the medication 'off' state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum-VP-mediodorsal thalamus-cortex network may be associated with pathophysiological mechanisms of PD-LID.

Increased brain iron in patients with thyroid-associated ophthalmopathy: a whole-brain analysis.

To investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM). Forty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs. Compared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%). Patients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO.

A new 3D phase unwrapping method by region partitioning and local polynomial modeling in abdominal quantitative susceptibility mapping.

Accurate phase unwrapping is a critical prerequisite for successful applications in phase-related MRI, including quantitative susceptibility mapping (QSM) and susceptibility weighted imaging. However, many existing 3D phase unwrapping algorithms face challenges in the presence of severe noise, rapidly changing phase, and open-end cutline. In this study, we introduce a novel 3D phase unwrapping approach utilizing region partitioning and a local polynomial model. Initially, the method leverages phase partitioning to create initial regions. Noisy voxels connecting areas within these regions are excluded and grouped into residual voxels. The connected regions within the region of interest are then reidentified and categorized into blocks and residual voxels based on voxel count thresholds. Subsequently, the method sequentially performs inter-block and residual voxel phase unwrapping using the local polynomial model. The proposed method was evaluated on simulation and in vivo abdominal QSM data, and was compared with the classical Region-growing, Laplacian_based, Graph-cut, and PRELUDE methods. Simulation experiments, conducted under different signal-to-noise ratios and phase change levels, consistently demonstrate that the proposed method achieves accurate unwrapping results, with mean error ratios not exceeding 0.01%. In contrast, the error ratios of Region-growing (N/A, 84.47%), Laplacian_based (20.65%, N/A), Graph-cut (2.26%, 20.71%), and PRELUDE (4.28%, 10.33%) methods are all substantially higher than those of the proposed method. In vivo abdominal QSM experiments further confirm the effectiveness of the proposed method in unwrapping phase data and successfully reconstructing susceptibility maps, even in scenarios with significant noise, rapidly changing phase, and open-end cutline in a large field of view. The proposed method demonstrates robust and accurate phase unwrapping capabilities, positioning it as a promising option for abdominal QSM applications.

Cerebral Oxygen Metabolism Improves Following Hematopoietic Cell Transplantation in Children with Sickle Cell Disease

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with sickle cell disease (SCD). It is often recommended for patients with severe SCD, including those at risk of, or with a history of stroke. There has been limited investigation into the direct impact of HCT on cerebral hemodynamics. Quantitative biomarkers of cerebral hemodynamics, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), can provide an objective assessment of therapeutic efficacy of HCT as well as other emerging therapies. We have previously shown that CBF improves after HCT in patients with SCD (Sharma A, et al. Suppl 1, Blood 2021). Here, we performed a prospective evaluation using magnetic resonance imaging (MRI) to measure the OEF of the whole brain and the superior sagittal sinus (SSS), to compare cerebral oxygen metabolism in SCD patients before and after HCT. Methods: We performed anatomical and hemodynamic MRI of the brain prior to, and at 6 months after HCT in children with SCD undergoing a reduced intensity conditioning based HCT on a clinical trial (NCT04362293). Patients were receiving either hydroxyurea (HU) or chronic transfusion therapy (CTT) before HCT. MRI brain scanning was performed for all patients in a 3 Tesla MRI imaging system (Siemens MAGNETOM Prisma, Erlangen, Germany) with a 16-channel phased-array coil. Quantitative susceptibility map (QSM) imaging was performed through a 3D multi-echo gradient echo sequence with flow compensation and reconstructed with the morphology-enabled dipole inversion (MEDI) method (Liu T, et al. MRM 2013). The oxygen extraction fraction was calculated utilizing the established formula incorporating clinically measured hematocrit, tissue susceptibility, and hemoglobin susceptibility values quantified through quantitative susceptibility mapping (QSM), as previously delineated (Fan A, et al. JCBFM 2020) for the segmented vessels from the whole brain and the SSS. Results: The median age at HCT was 15.6 years (N=11). Hematocrit as well as global and regional (SSS) OEF of the patients were quantified and compared between baseline and at 6 months after HCT (Fig 1). All patients experienced a decrease in OEF after HCT. We then stratified the patients into those who were receiving HU or CTT prior to HCT. In patients receiving HU prior to HCT (n=7), there was a small decrease in OEF for the whole brain (42.4% vs. 39.9%, P = 0.40) and SSS (33.1% vs. 31.3%, P =0.12) at 6 months after HCT compared to baseline. However, in patients receiving CTT prior to HCT (n=4) both the global OEF (50.0% vs. 34.4 %, P &amp;lt; 0.01) and regional OEF (31.8% vs. 26.7 %, P &amp;lt; 0.05) decreased significantly at 6 months after HCT. All patients exhibited an increased hematocrit following HCT (Fig 2). Specifically, the HU cohort improved from a mean of 27.4% to 37.5% ( P&amp;lt;0.01), while the CTT cohort increased from 26.2% to 39.6% ( P&amp;lt;0.01) after HCT. Conclusions: Our results demonstrate the feasibility of global and regional OEF quantification using MRI in patients undergoing HCT for SCD. We observed that the OEF of the whole brain and SSS exhibited a similar downward trend after HCT in patients receiving either HU or CTT. This indicates an overall improvement in oxygen delivery after HCT. OEF decrease was marked after HCT in the CTT group, suggesting that HCT provided better cerebral hemodynamic outcomes than at baseline for this group. In contrast, the cohort of patients receiving HU showed a subtle decrease in OEF after HCT, perhaps implying that these patients had milder cerebral hemodynamic compromise than the CTT group. Both pretreatment groups demonstrated significantly higher hemoglobin concentrations after HCT compared to before treatment which may have contributed to the improvement in OEF. Our study presents objective physiologic comparisons of different clinical therapies on cerebral hemodynamics, providing early data on the effects of cerebral oxygen delivery in pediatric patients with SCD. Further studies with larger patient numbers are warranted to confirm the trends observed in oxygen metabolism and understand the mechanisms underlying differential responses to HCT and other disease-modifying therapies. These imaging biomarkers may also help assess different genetic therapies currently in development.