Detection of pathological contrast enhancement with synthetic brain imaging from quantitative multiparametric MRI.

BACKGROUND AND PURPOSE: We aimed to test whether synthetic T1-weighted imaging derived from a post-contrast Quantitative Transient-state Imaging (QTI) acquisition enabled revealing pathological contrast enhancement in intracranial lesions. METHODS: The analysis included 141 patients who underwent a 3 Tesla-MRI brain exam with intravenous contrast media administration, with the post-contrast acquisition protocol comprising a three-dimensional fast spoiled gradient echo (FSPGR) sequence and a QTI acquisition. Synthetic T1-weighted images were generated from QTI-derived quantitative maps of relaxation times and proton density. Two neuroradiologists assessed synthetic and conventional post-contrast T1-weighted images for the presence and pattern of pathological contrast enhancement in intracranial lesions. Enhancement volumes were quantitatively compared. RESULTS: Using conventional imaging as a reference, synthetic T1-weighted imaging was 93% sensitive in revealing the presence of contrast enhancing lesions. The agreement for the presence/absence of contrast enhancement was almost perfect both between readers (k = 1 for both conventional and synthetic imaging) and between sequences (k = 0.98 for both readers). In 91% of lesions, synthetic T1-weighted imaging showed the same pattern of contrast enhancement visible in conventional imaging. Differences in enhancement pattern in the remaining lesions can be due to the lower spatial resolution and the longer acquisition delay from contrast media administration of QTI compared to FSPGR. Overall, enhancement volumes appeared larger in synthetic imaging. CONCLUSIONS: QTI-derived post-contrast synthetic T1-weighted imaging captures pathological contrast enhancement in most intracranial enhancing lesions. Further comparative studies employing quantitative imaging with higher spatial resolution is needed to support our data and explore possible future applications in clinical trials.

Quantitative T1 mapping detects blood-brain barrier breakdown in apparently non-enhancing multiple sclerosis lesions.

OBJECTIVES: The disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs). MATERIALS AND METHODS: Thirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging. RESULTS: Mean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients. CONCLUSIONS: QTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.

Motor cortical patterns of upper motor neuron pathology in amyotrophic lateral sclerosis: A 3 T MRI study with iron-sensitive sequences.

BACKGROUND: Patterns of initiation and propagation of disease in Amyotrophic Lateral Sclerosis (ALS) are still partly unknown. Single or multiple foci of neurodegeneration followed by disease diffusion to contiguous or connected regions have been proposed as mechanisms underlying symptom occurrence. Here, we investigated cortical patterns of upper motor neuron (UMN) pathology in ALS using iron-sensitive MR imaging. METHODS: Signal intensity and magnetic susceptibility of the primary motor cortex (M1), which are associated with clinical UMN burden and neuroinflammation, were assessed in 78 ALS patients using respectively T2*-weighted images and Quantitative Susceptibility Maps. The signal intensity of the whole M1 and each of its functional regions was rated as normal or reduced, and the magnetic susceptibility of each M1 region was measured. RESULTS: The highest frequencies of T2* hypointensity were found in M1 regions associated with the body sites of symptom onset. Homologous M1 regions were both hypointense in 80-93 % of patients with cortical abnormalities, and magnetic susceptibility values measured in homologous M1 regions were strongly correlated with each other (ρ = 0.88; p < 0.0001). In some cases, the T2* hypointensity was detectable in two non-contiguous M1 regions but spared the cortex in between. CONCLUSIONS: M1 regions associated with the body site of onset are frequently affected at imaging. The simultaneous involvement of both homologous M1 regions is frequent, followed by that of adjacent regions; the affection of non-contiguous regions, instead, seems rare. This type of cortical involvement suggests the interhemispheric connections as one of the preferential paths for the UMN pathology diffusion in ALS.

Distribution Indices of Magnetic Susceptibility Values in the Primary Motor Cortex Enable to Classify Patients with Amyotrophic Lateral Sclerosis.

Quantitative Susceptibility Mapping (QSM) can measure iron concentration increase in the primary motor cortex (M1) of patients with Amyotrophic Lateral Sclerosis (ALS). However, such alteration is confined to only specific regions interested by upper motor neuron pathology; therefore, mean QSM values in the entire M1 have limited diagnostic accuracy in discriminating between ALS patients and control subjects. This study investigates the diagnostic accuracy of a broader set of M1 QSM distribution indices in classifying ALS patients and controls. Mean, standard deviation, skewness and kurtosis of M1 QSM values were used either individually or as combined predictors in support vector machines. The classification performance was compared to that obtained by the radiological assessment of T2* signal hypo-intensity of M1 in susceptibility-weighted MRI. The least informative index for the classification of ALS patients and controls was the subject's mean QSM value in M1. The highest diagnostic performance was obtained when all the distribution indices of positive QSM values in M1 were considered, which yielded a diagnostic accuracy of 0.90, with sensitivity = 0.89 and specificity = 1. The radiological assessment of M1 yielded a diagnostic accuracy of 0.79, with sensitivity = 0.76 and specificity = 0.90. The joint evaluation of QSM distribution indices could support the clinical examination in ALS diagnosis and patient monitoring.

Morphometric imaging and quantitative susceptibility mapping as complementary tools in the diagnosis of parkinsonisms.

BACKGROUND AND PURPOSE: In the quest for in vivo diagnostic biomarkers to discriminate Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA, mainly p phenotype), many advanced magnetic resonance imaging (MRI) techniques have been studied. Morphometric indices, such as the Magnetic Resonance Parkinsonism Index (MRPI), demonstrated high diagnostic value in the comparison between PD and PSP. The potential of quantitative susceptibility mapping (QSM) was hypothesized, as increased magnetic susceptibility (Δχ) was reported in the red nucleus (RN) and medial part of the substantia nigra (SNImed) of PSP patients and in the putamen of MSA patients. However, disease-specific susceptibility values for relevant regions of interest are yet to be identified. The aims of the study were to evaluate the diagnostic potential of a multimodal MRI protocol combining morphometric and QSM imaging in patients with determined parkinsonisms and to explore its value in a population of undetermined cases. METHOD: Patients with suspected degenerative parkinsonism underwent clinical evaluation, 3 T brain MRI and clinical follow-up. The MRPI was manually calculated on T1-weighted images. QSM maps were generated from 3D multi-echo T2*-weighted sequences. RESULTS: In determined cases the morphometric evaluation confirmed optimal diagnostic accuracy in the comparison between PD and PSP but failed to discriminate PD from MSA-p. Significant nigral and extranigral differences were found with QSM. RN Δχ showed excellent diagnostic accuracy in the comparison between PD and PSP and good accuracy in the comparison of PD and MSA-p. Optimal susceptibility cut-off values of RN and SNImed were tested in undetermined cases in addition to MRPI. CONCLUSIONS: A combined use of morphometric imaging and QSM could improve the diagnostic phase of degenerative parkinsonisms.

Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook.

Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described, and new sequencing techniques such as Next-generation sequencing are available. Brain imaging is significant for the detection of these diseases. Since it is often performed at an initial stage, an MRI is a key to selecting patients for genetic testing and for interpreting nextgeneration sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. In this review, we aim to provide neurologists and stroke physicians with an up-to-date overview of the current neuroimaging knowledge on monogenic small vessel diseases.

Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

OBJECTIVES: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. METHODS: We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated. RESULTS: The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases). CONCLUSIONS: Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients. KEY POINTS: • The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence. • Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity. • The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes.

Is DAT imaging abnormality in normal pressure hydrocephalus always suggestive of degeneration?

Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage. 123I-FP-CIT-SPECT was believed to be helpful in this regard, however its role in predicting surgical outcome has been disputed. We illustrate a patient presented with gait disturbance, urinary incontinence, and asymmetrical parkinsonian signs, who underwent a 3T brain MRI and a 123I-FP-CIT-SPECT. VPS was performed. The patient repeated a 123I-FP-CIT-SPECT, 18 months after the operation, and was clinically followed up for 24 months. Our patient displayed clinical and radiological criteria for iNPH and an abnormal asymmetrical uptake in 123I-FP-CIT-SPECT, consistent with her asymmetrical parkinsonism. However, the organization of the substantia nigra studied with iron-sensitive sequences in 3T brain MRI scan appeared intact. The patient revealed an improvement both clinically and in 123I-FP-CIT-SPECT at postsurgical follow-up. Our report suggests that abnormal 123I-FP-CIT-SPECT may not necessarily reveal an overlap with neurodegenerative parkinsonism; its partial reversibility may suggest that the mechanical effect exerted on the striatum by ventriculomegaly ultimately leads to downregulation of dopaminergic transporters which may improve after VPS.

Evolution, Predictors, and Neurocognitive Effects of Silent Cerebral Embolism During Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to assess the characteristics, predictors, evolution, and neurocognitive effects of silent cerebral ischemic lesions (SCILs). BACKGROUND: Most patients undergoing transcatheter aortic valve replacement (TAVR) develop SCILs detectable on magnetic resonance imaging (MRI). The natural history and clinical relevance of SCILs are not well established. METHODS: Cerebral MRI was performed within 7 days before TAVR to assess baseline status and age-related white matter change score. MRI was repeated post-operatively to assess the occurrence, location, number, and dimensions of SCILs. Patients developing SCILs underwent a third MRI examination at 3- to 5-month follow-up. A neurocognitive evaluation was performed before TAVR, at discharge, and at 3-month follow-up. RESULTS: Of the 117 patients enrolled, 96 underwent post-procedural MRI; SCILs were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, a median diameter of 4.5 mm, and a median total volume of 140 mm3. Independent predictors of SCIL occurrence were higher baseline age-related white matter change score and the use of self-expanding or mechanically expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of post-procedural SCILs evolved into gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVR and with lower recovery at follow-up. CONCLUSIONS: SCILs occur in the vast majority of patients undergoing TAVR and are predicted by more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCILs disappear within months, their occurrence has a limited but significant impact on neurocognitive function.

Quantitative susceptibility mapping in atypical Parkinsonisms.

BACKGROUND AND PURPOSE: Differential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), remains challenging. The low sensitivity of macroscopic findings at imaging might limit early diagnosis. The availability of iron-sensitive MR techniques and high magnetic field MR scanners provides new insights in evaluating brain structures in degenerative parkinsonisms. Quantitative Susceptibility Mapping (QSM) allows quantifying tissue iron content and could be sensitive to microstructural abnormalities which precede the appearence of regional atrophy. We measured the magnetic susceptibility (χ) of nigral and extranigral regions in patients with PD, PSP and MSA to evaluate the potential utility of the QSM technique for differential diagnosis. MATERIALS AND METHODS: 65 patients (36 PD, 14 MSA, 15 PSP) underwent clinical and radiological evaluation with 3 T MRI. QSM maps were obtained from GRE sequences. ROI were drawn on substantia nigra (SN), red nucleus (RN), subthalamic nucleus (STN), putamen, globus pallidus and caudate. χ values were compared to detect inter-group differences. RESULTS: The highest diagnostic accuracy for PSP (area under the ROC curve, AUC, range 0.9-0.7) was observed for increased χ values in RN, STN and medial part of SN whereas in MSA (AUC range 0.8-0.7) iron deposition was significantly higher in the putamen, according to the patterns of pathological involvement that characterize the different diseases. CONCLUSION: QSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes.

MRI cortical feature of bulbar impairment in patients with amyotrophic lateral sclerosis.

The decline of voluntary bulbar functions such as speech and swallowing are among the clinical manifestations of amyotrophic lateral sclerosis (ALS) influencing a worst prognosis. Differential diagnosis between the contribution of upper motor neuron (UMN) and lower motor neuron degeneration to the bulbar impairment is often hard. Thinning and T2* hypointensity of the primary motor cortex have been recently suggested as possible MRI markers of UMN impairment in ALS patients, but little research has purposely targeted the orofacial region of the primary motor cortex (fM1). With the aim of finding an MRI marker of UMN impairment responsible for bulbar dysfunction, we investigated the T2* signal intensity of fM1 and the relationship with bulbar impairment in ALS patients. Fifty-five ALS patients were examined with 3 T MRI. Their fM1 was evaluated both qualitatively in terms of T2* signal intensity and quantitatively by measuring its magnetic susceptibility with Quantitative Susceptibility Mapping (QSM). Bulbar functions were assessed clinically, by neurological examination and using the items 1-3 of the ALSFRS-R, and with neurophysiological tests. The marked hypointensity of fM1 was detected in 25% of ALS patients, including all patients with bulbar onset, and was 74% sensitive, 100% specific and 91% accurate in diagnosing functional bulbar impairment. Such hypointensity involved the middle and ventral part of fM1 and was usually visible in both hemispheres. The magnetic susceptibility was significantly higher in patients with marked fM1 hypointensity than in the other patients (p ≤ .001). The relationship with clinical and neurophysiological data suggests that such feature could be a marker of UMN degeneration for voluntary bulbar functions.