Theranostic nanoagents are promising for precision medicine. However, biodegradable nanoagents with the ability for photoacoustic (PA) imaging guided photothermal therapy (PTT) are rare. We herein report the development of biodegradable semiconducting polymer nanoparticles (SPNs) with enhanced PA and PTT efficacy for cancer therapy. The design capitalizes on the enzymatically oxidizable nature of vinylene bonds in conjunction with polymer chemistry to synthesize a biodegradable semiconducting polymer (DPPV) and transform it into water-soluble nanoparticles (SPNV). As compared with its counterpart SPN (SPNT), the presence of vinylene bonds within the polymer backbone also endows SPNV with a significantly enhanced mass absorption coefficient (1.3-fold) and photothermal conversion efficacy (2.4-fold). As such, SPNV provides the PA signals and the photothermal maximum temperature higher than SPNT, allowing detection and photothermal ablation of tumors in living mice in a more sensitive and effective way. Our study thus reveals a general molecular design to enhance the biodegradability of optically active polymer nanoparticles while dramatically elevating their imaging and therapeutic capabilities.

The recovery process of COVID-19 patients is unclear. Some recovered patients complain of continued shortness of breath. Vasculopathy has been reported in COVID-19, stressing the importance of probing microstructure and function of lungs at the alveolar-capillary interface. While CT detects structural abnormalities, little is known about the impact of disease on lung function. 129Xe MRI is a technique uniquely capable of assessing ventilation, microstructure and gas exchange. Using 129Xe MRI, we found COVID-19 patients have higher ventilation defects percentage (5.9% vs 3.7%), unchanged microstructure, longer gas-blood exchange time (43.5 ms vs 32.5 ms), and reduced RBC/TP (0.279 vs 0.330) compared with healthy subjects. These findings suggest regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished. This study establishes the feasibility of localized lung function measurement in COVID-19 patients. Such readouts could be useful as a supplement to structural imaging.

Excess iron deposition in the brain often causes oxidative stress-related damage and necrosis of dopaminergic neurons in the substantia nigra and has been reported to be one of the major vulnerability factors in Parkinson's disease (PD). Iron chelation therapy using deferoxamine (DFO) may inhibit this nigrostriatal degeneration and prevent the progress of PD. However, DFO shows very short half-life in vivo and hardly penetrates the blood brain barrier (BBB). Hence, it is of great interest to develop DFO formulations for safe and efficient intracerebral drug delivery. Herein, we report a polymeric nanoparticle system modified with brain-targeting peptide rabies virus glycoprotein (RVG) 29 that can intracerebrally deliver DFO. The nanoparticle system penetrates the BBB possibly through specific receptor-mediated endocytosis triggered by the RVG29 peptide. Administration of these nanoparticles significantly decreased iron content and oxidative stress levels in the substantia nigra and striatum of PD mice and effectively reduced their dopaminergic neuron damage and as reversed their neurobehavioral deficits, without causing any overt adverse effects in the brain or other organs. This DFO-based nanoformulation holds great promise for delivery of DFO into the brain and for realizing iron chelation therapy in PD treatment.

Although excellent intra- and interscanner reliability and reproducibility could support the feasibility of cross-site pooling of ASL data, pCASL with multiple PLDs may better assess the CBF of the human brain.

BackgroundAuditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified.MethodsWe performed whole-exome sequencing on DNA samples from the AUNX1 family and another small phenotypically similar but unrelated ANSD family.ResultsWe identified two missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1 family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD identified 9 more missense mutations in AIFM1. Bioinformatics analysis and expression studies support this gene as being causative of ANSD.ConclusionsVariants in AIFM1 gene are a common cause of familial and sporadic ANSD and provide insight into the expanded spectrum of AIFM1-associated diseases. The finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD implies that MRI may be of value in localising the site of lesion and suggests that cochlea implantation in these patients may have limited success.

ObjectivesWe hypothesized that three-dimensional pseudocontinuous arterial spin labelling (pCASL) may have similar efficacy in astrocytic tumour grading as dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI), and the grading accuracy may be further improved when combined with apparent diffusion coefficient (ADC) values.MethodsForty-three patients with astrocytic tumours were studied using diffusion weighted imaging (DWI), pCASL, and DSC-PWI. Histograms of ADC and normalized tumour cerebral blood flow values (nCBF on pCASL and nrCBF on DSC-PWI) were measured and analyzed.ResultsThe mean 10 % ADC value was the DWI parameter that provided the best differentiation between low-grade astrocytoma (LGA) and high-grade astrocytoma (HGA). The nCBF and nrCBF (1.810 ± 0.979 and 2.070 ± 1.048) in LGA were significantly lower than those (4.505 ± 2.270 and 5.922 ± 2.630) in HGA. For differentiation between LGA and HGA, the cutoff values of 0.764 × 10-3 mm2/s for mean 10 % ADC, 2.374 for nCBF, and 3.464 for nrCBF provided the optimal accuracy (74.4 %, 86.1 %, and 88.6 %, respectively). Combining the ADC values with nCBF or nrCBF could further improve the grading accuracy to 97.7 % or 95.3 %, respectively.ConclusionspCASL is an alternative to DSC-PWI for astrocytic tumour grading. The combination of DWI and contrast-free pCASL offers a valuable choice in patients with risk factors.Key Points• pCASL shows positive correlation with DSC-PWI in astrocytic tumour grading.• ADC values based on ADC histograms can be an objective method.• Combination of DWI and pCASL or DSC-PWI can improve grading accuracy.

Background and purpose Three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) with multiple post-labeling delays (PLDs) has been used to assess cerebral blood flow (CBF). We used this modality to estimate antegrade and collateral flow in patients with unilateral middle cerebral artery (MCA) stenosis. Methods Consecutive patients with unilateral MCA 50% to 99% stenosis at two centers underwent pCASL with a PLD of 1.5s and 2.5s. Mean CBF of bilateral MCA territory at the PLD 1.5s and 2.5s were measured. Early-arriving flow proportion was defined as [CBF 1.5s at lesion side/CBF 2.5s at normal side] × 100%. Late-arriving retrograde flow proportion was defined as [(CBF 2.5s minus CBF 1.5s) at lesion side minus (CBF 2.5s minus CBF 1.5s) at normal side]/CBF 2.5s at normal side × 100%. Antegrade and collateral scales were evaluated in patients with conventional angiography. Spearman correlation coefficients were calculated between early-arriving flow and late-arriving retrograde flow proportions on ASL and antegrade and collateral scales on conventional angiography, respectively. Results Forty-one patients (46.0±12.0 years) were enrolled. The mean early-arriving flow proportion was 78.3%±14.9%. The mean late-arriving retrograde flow proportion was 16.1%±10.2%. In 21 patients with conventional angiography, Spearman correlation coefficient was 0.53 (95%CI 0.11–0.79) between antegrade grade and early-arriving flow proportion (p=0.01) and 0.81 (95%CI 0.56–0.92) between collateral grade and late-arriving retrograde flow proportion (p<0.0001). Conclusion Three-dimensional pCASL with two-PLD may provide an empirical approach for estimating antegrade and collateral flow in patients with unilateral MCA stenosis.

Meningeal melanocytoma is an uncommon pigmented neoplasm that affects the CNS and develops in the cranial and spinal leptomeninges. Here we report on a case of malignant transformation of intracranial supratentorial meningeal melanocytoma which recurred after 3 years as malignant melanoma. This case demonstrates that the biological behavior of melanocytoma is uncertain and that these lesions may recur as malignant melanoma.