Detecting small pulmonary nodules with spiral ultrashort echo time sequences in 1.5 T MRI.

OBJECTIVE: This study investigated ultrashort echo time (UTE) sequences in 1.5 T magnetic resonance imaging (MRI) for small lung nodule detection. MATERIALS AND METHODS: A total of 120 patients with 165 small lung nodules before video-associated thoracoscopic resection were enrolled. MRI sequences included conventional volumetric interpolated breath-hold examination (VIBE, scan time 16 s), spiral UTE (TE 0.05 ms) with free-breathing (scan time 3.5-5 min), and breath-hold sequences (scan time 20 s). Chest CT provided a standard reference for nodule size and morphology. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. RESULTS: The nodule detection rate was significantly higher in spiral UTE free-breathing (> 78%, p < 0.05) and breath-hold sequences (> 75%, p < 0.05) compared with conventional VIBE (> 55%), reaching 100% when nodule size was > 16 mm, and reaching 95% when nodules were in solid morphology, regardless of size. The inter-sequence reliability between free-breathing and breath-hold spiral UTE was good (κ > 0.80). Inter-reader agreement was also high (κ > 0.77) for spiral UTE sequences. Nodule size measurements were consistent between CT and spiral UTE MRI, with a minimal bias up to 0.2 mm. DISCUSSION: Spiral UTE sequences detect small lung nodules that warrant surgery, offers realistic scan times for clinical work, and could be implemented as part of routine lung MRI.

Is a timely assessment of the hematocrit necessary for cardiovascular magnetic resonance-derived extracellular volume measurements?

BACKGROUND: Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) requires a hematocrit (Hct) to correct contrast volume distributions in blood. However, the timely assessment of Hct can be challenging and has limited the routine clinical application of ECV. The goal of the present study was to evaluate whether ECV measurements lead to significant error if a venous Hct was unavailable on the day of CMR. METHODS: 109 patients with CMR T1 mapping and two venous Hcts (Hct0: a Hct from the day of CMR, and Hct1: a Hct from a different day) were retrospectively identified. A synthetic Hct (Hctsyn) derived from native blood T1 was also assessed. The study used two different ECV methods, (1) a conventional method in which ECV was estimated from native and postcontrast T1 maps using a region-based method, and (2) an inline method in which ECV was directly measured from inline ECV mapping. ECVs measured with Hct0, Hct1, and Hctsyn were compared for each method, and the reference ECV (ECV0) was defined using the Hct0. The error between synthetic (ECVsyn) and ECV0was analyzed for the two ECV methods. RESULTS: ECV measured using Hct1 and Hctsyn were significantly correlated with ECV0 for each method. No significant differences were observed between ECV0 and ECV measured with Hct1 (ECV1; 28.4 ± 6.6% vs. 28.3 ± 6.1%, p = 0.789) and between ECV0 and ECV calculated with Hctsyn (ECVsyn; 28.4 ± 6.6% vs. 28.2 ± 6.2%, p = 0.45) using the conventional method. Similarly, ECV0 was not significantly different from ECV1 (28.5 ± 6.7% vs. 28.5 ± 6.2, p = 0.801) and ECVsyn (28.5 ± 6.7% vs. 28.4 ± 6.0, p = 0.974) using inline method. ECVsyn values revealed relatively large discrepancies in patients with lower Hcts compared with those with higher Hcts. CONCLUSIONS: Venous Hcts measured on a different day from that of the CMR examination can still be used to measure ECV. ECVsyn can provide an alternative method to quantify ECV without needing a blood sample, but significant ECV errors occur in patients with severe anemia.

Applying Compressed Sensing Volumetric Interpolated Breath-Hold Examination and Spiral Ultrashort Echo Time Sequences for Lung Nodule Detection in MRI.

This prospective study aimed to investigate the ability of spiral ultrashort echo time (UTE) and compressed sensing volumetric interpolated breath-hold examination (CS-VIBE) sequences in magnetic resonance imaging (MRI) compared to conventional VIBE and chest computed tomography (CT) in terms of image quality and small nodule detection. Patients with small lung nodules scheduled for video-assisted thoracoscopic surgery (VATS) for lung wedge resection were prospectively enrolled. Each patient underwent non-contrast chest CT and non-contrast MRI on the same day prior to thoracic surgery. The chest CT was performed to obtain a standard reference for nodule size, location, and morphology. The chest MRI included breath-hold conventional VIBE and CS-VIBE with scanning durations of 11 and 13 s, respectively, and free-breathing spiral UTE for 3.5-5 min. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and normal structure visualizations were measured to evaluate MRI quality. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. Inter-reader and inter-modality reliability analyses were performed using the Cohen κ statistic and the nodule size comparison was performed using Bland-Altman plots. Among 96 pulmonary nodules requiring surgery, the average nodule diameter was 7.7 ± 3.9 mm (range: 4-20 mm); of the 73 resected nodules, most were invasive cancer (74%) or pre-invasive carcinoma in situ (15%). Both spiral UTE and CS-VIBE images achieved significantly higher overall image quality scores, SNRs, and CNRs than conventional VIBE. Spiral UTE (81%) and CS-VIBE (83%) achieved a higher lung nodule detection rate than conventional VIBE (53%). Specifically, the nodule detection rate for spiral UTE and CS-VIBE reached 95% and 100% for nodules >8 and >10 mm, respectively. A 90% detection rate was achieved for nodules of all sizes with a part-solid or solid morphology. Spiral UTE and CS-VIBE under-estimated the nodule size by 0.2 ± 1.4 mm with 95% limits of agreement from -2.6 to 2.9 mm and by 0.2 ± 1.7 mm with 95% limits of agreement from -3.3 to 3.5 mm, respectively, compared to the reference CT. In conclusion, chest CT remains the gold standard for lung nodule detection due to its high image resolutions. Both spiral UTE and CS-VIBE MRI could detect small lung nodules requiring surgery and could be considered a potential alternative to chest CT; however, their clinical application requires further investigation.

CMR-derived ECVs vary with myocardial region and associate with the regional wall thickness.

This study was designed to identify whether the position and size of the region of interest (ROI) influence extracellular volume fraction (ECV) measurements. Patients with localized (n = 203) or infiltrative (n = 215) cardiomyopathies and 36 normal controls were enrolled in this study. ECV measurements at 4 different regions, including the anterior, septal, posterior and lateral wall regions, were measured, and all groups were compared. Regional ECV was correlated with the corresponding regional wall thickness. The diagnostic power to differentiate the myocardial abnormalities was evaluated for each myocardial region. ECVs measured using five different ROI sizes within each myocardial region were compared. Our results showed that ECVs varied among the myocardial regions, and this variation was significantly associated with regional wall thicknesses. For the detection of myocardial abnormalities, regional ECV revealed similar results as ECV derived from the whole region except for the anterior region. No significant difference was found in the ECVs measured using the five different ROI sizes. In conclusion, CMR-derived ECVs vary with myocardial region, and this variation is significantly associated with the regional wall thickness. In contrast, the measured size of the ROI has less of an effect on the ECV.

CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain.

Neural circuit formation is a critical process in brain development. Axon guidance molecules, their receptors, and intracellular mediators are important to establish neural circuits. Collapsin response mediator proteins (CRMPs) are known intercellular mediators of a number of repulsive guidance molecules. Studies of mutant mice suggest roles of CRMPs in dendrite development. However, molecular mechanisms of CRMP-mediated dendritic development remain to elucidate. In this study, we show abnormal orientation of basal dendrites (extension to deeper side) of layer V pyramidal neurons in the cerebral cortex of CRMP4-/- mice. Moreover, we observed severe abnormality in orientation of the basal dendrites of these neurons in double knockout of CRMP1 and 4, suggesting redundant functions of these two genes. Redundant gene functions were also observed in proximal bifurcation phenotype in apical dendrites of hippocampal CA1 pyramidal neurons. These results indicate that CRMP1 and CRMP4 regulate proper orientation of the basal dendrites of layer V neurons in the cerebral cortex.

Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons.

The neural circuit in the hippocampus is important for higher brain functions. Dendrites of CA1 pyramidal neurons mainly receive input from the axons of CA3 pyramidal neurons in this neural circuit. A CA1 pyramidal neuron has a single apical dendrite and multiple basal dendrites. In wild-type mice, most of CA1 pyramidal neurons extend a single trunk, or alternatively, the apical dendrite bifurcates into two daughter trunks at the stratum radiatum layer. We previously reported the proximal bifurcation phenotype in Sema3A-/-, p35-/-, and CRMP4-/- mice. Cdk5/p35 phosphorylates CRMP2 at Ser522, and inhibition of this phosphorylation suppressed Sema3A-induced growth cone collapse. In this study, we analyzed the bifurcation points of the apical dendrites of hippocampal CA1 pyramidal neurons in CRMP2KI/KI mice in which the Cdk5/p35-phosphorylation site Ser522 was mutated into an Ala residue. The proximal bifurcation phenotype was not observed in CRMP2KI/KI mice; however, severe proximal bifurcation of apical dendrites was found in CRMP2KI/KI;CRMP4-/- mice. Cultured hippocampal neurons from CRMP2KI/KI and CRMP2KI/KI;CRMP4-/- embryos showed an increased number of dendritic branching points compared to those from wild-type embryos. Sema3A increased the number of branching points and the total length of dendrites in wild-type hippocampal neurons, but these effects of Sema3A for dendrites were not observed in CRMP2KI/KI and CRMP2KI/KI;CRMP4-/-hippocampal neurons. Binding of CRMP2 to tubulin increased in both CRMP2KI/KI and CRMP2KI/KI:CRMP4-/- brain lysates. These results suggest that CRMP2 and CRMP4 synergistically regulate dendritic development, and CRMP2 phosphorylation is critical for proper bifurcation of apical dendrite of CA1 pyramidal neurons.

Pax6 exerts regional control of cortical progenitor proliferation via direct repression of Cdk6 and hypophosphorylation of pRb.

The mechanisms by which early spatiotemporal expression patterns of transcription factors such as Pax6 regulate cortical progenitors in a region-specific manner are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6⁺/⁺ and Pax6⁻/⁻ cortices and identified many negatively regulated cell-cycle genes, including Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes that directly promote the mechanics of the cell cycle, and we found that Pax6 inhibits pRb phosphorylation and represses genes involved in DNA replication. Our results indicate that Pax6's modulation of cortical progenitor cell cycles is regional and direct.

CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus.

Collapsin response mediator proteins (CRMPs) are a family of cytosolic phosphoproteins that consist of 5 members (CRMP 1-5). CRMP2 and CRMP4 regulate neurite outgrowth by binding to tubulin heterodimers, resulting in the assembly of microtubules. CRMP2 also mediates the growth cone collapse response to the repulsive guidance molecule semaphorin-3A (Sema3A). However, the role of CRMP4 in Sema3A signaling and its function in the developing mouse brain remain unclear. We generated CRMP4-/- mice in order to study the in vivo function of CRMP4 and identified a phenotype of proximal bifurcation of apical dendrites in the CA1 pyramidal neurons of CRMP4-/- mice. We also observed increased dendritic branching in cultured CRMP4-/- hippocampal neurons as well as in cultured cortical neurons treated with CRMP4 shRNA. Sema3A induces extension and branching of the dendrites of hippocampal neurons; however, these inductions were compromised in the CRMP4-/- hippocampal neurons. These results suggest that CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus and that this is partly dependent on Sema3A signaling.