ABSTRACT
Objetivo: Nuestro principal objetivo es el de comparar la capacidad para detectar las drusas del disco óptico (DDO) utilizando diversas técnicas de imágenes no-invasivas, incluida la novedosa técnica de imagen de retromodo (RMI). Como segundo objetivo analizamos las características morfológicas de las DDO bajo esta última técnica. Materiales y métodos: Este estudio incluyó un total de 7 pacientes con DDO bilaterales, obteniendo un total de 14 ojos analizados. Se utilizaron técnicas no invasivas de imágenes multimodales, que incluyeron fotografía multicolor del fondo de ojo (MC), reflectancia en infrarrojo (NIR), autofluorescencia en luz verde y en luz azul (G-FAF y B-FAF, respectivamente) y RMI. La FAF se utilizó como el método principal para el diagnóstico de DDO. Dos observadores realizaron las comparaciones, obteniendo las tasas de detección de cada uno de los métodos. Las mediciones cuantitativas de las DDO incluyeron el número, el perímetro (P) y el área (A) de las DDO identificadas mediante la técnica de RMI. Resultado: La edad promedio de los pacientes incluidos fue de 49,28±23,16 años; 5 de los 7 pacientes fueron de sexo masculino. La técnica de RMI pudo detectar DDO en todos los casos, con una sensibilidad del 100%, en comparación con MC (sensibilidad del 60,71%), NIR (sensibilidad del 60,71%), B-FAF (sensibilidad del 100%), G-FAF (sensibilidad del 100%). RMI fue la única técnica de imagen capaz de evaluar morfológica y cuantitativamente las DDO. Conclusiones: RMI es una prometedora modalidad no-invasiva de imagen para diagnosticar DDO superficiales, proporcionando información valiosa sobre la distribución, la ubicación y el tamaño de estas. Por lo tanto, mediante nuestros resultados sugerimos la incorporación de la novedosa técnica de RMI como una herramienta complementaria para el diagnóstico y el seguimiento de DDO en combinación con los otros métodos de imagen multimodales.(AU)
Objective: We aimed to compare the detectability of optic disc drusen (ODD), using various non-invasive imaging techniques, including the novel retro-mode imaging (RMI), as well as to analyze the morphological characteristics of ODD on RMI. Methods: This study involved 7 patients with bilateral ODD, totaling 14 eyes. Multimodal imaging techniques, including multicolor fundus photography (MC), near-infrared reflectance (NIR), green and blue light fundus autofluorescence (G-FAF and B-FAF, respectively), and RMI were used to examine the eyes. FAF was used as the primary method of identifying ODD, and each method's detection rate was compared by two observers. Quantitative measurements of ODD included the number of ODD visualized by the RMI technique, the perimeter (P) and area (A) of ODD were identified. Results: The average age of the patients included was 49.28±23.16 years, with 5 of the 7 being men. RMI was able to detect ODD in all cases, with a sensitivity of 100%, compared to MC (sensitivity 60.71%), NIR (sensitivity 60.71%), B-FAF (sensitivity 100%), G-FAF (sensitivity 100%). RMI was the only imaging technique capable of assessing ODD morphology and quantifying ODD. Conclusions: RMI is a promising imaging modality for diagnosing superficial ODD, providing valuable information on the distribution, location, and size of ODD. We suggest the incorporation of RMI as a complementary tool for diagnosing and monitoring ODD in combination with other multimodal imaging methods.(AU)
Subject(s)
Humans , Male , Female , Optic Disk , Optic Disk Drusen , Vision, Ocular , Ophthalmology , France , Retrospective StudiesABSTRACT
Background: In staging early rectal cancers (ERC), submucosal tumor depth is one of the most important features determining the possibility of local excision (LE). The micro-enema (Bisacodyl) induces submucosal edema and may hypothetically improve the visualization of tumor depth. Purpose: To test the diagnostic performance of MRI to identify ERC suitable for LE when adding a pre-procedural micro-enema and concurrent use of a modified classification system. Material and Methods: In this prospective study, we consecutively included 73 patients with newly diagnosed rectal tumors. Two experienced radiologists independently interpreted the MRI examinations, and diagnostic performance was calculated for local tumors eligible for LE (Tis-T1sm2, n = 43) and non-local tumors too advanced for LE (T1sm3-T3b, n = 30). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were registered for each reader. Inter- and intra-reader agreements were assessed by kappa statistics. Lymph node status was derived from the clinical MRI reports. Results: Reader1/reader2 achieved sensitivities of 93%/86%, specificities of 90%/83%, PPV of 93%/88%, and NPV of 90%/81%, respectively, for identifying tumors eligible for LE. Rates of overstaging of local tumors were 7% and 14% for the two readers, and kappa values for the inter- and intra-reader agreement were 0.69 and 0.80, respectively. For tumors ≤T2, all metastatic lymph nodes were smaller than 3 mm on histopathology. Conclusion: MRI after a rectal micro-enema and concurrent use of a modified staging system achieved good diagnostic performance to identify tumors suitable for LE. The rate of overstaging of local tumors was comparable to results reported in previous endorectal ultrasound (ERUS) studies.
ABSTRACT
J-aggregate is a promising strategy to enhance second near-infrared window (NIR-II) emission, while the controlled synthesis of J-aggregated NIR-II dyes is a huge challenge because of the lack of molecular design principle. Herein, bulk spiro[fluorene-9,9'-xanthene] functionalized benzobisthiadiazole-based NIR-II dyes (named BSFX-BBT and OSFX-BBT) are synthesized with different alkyl chains. The weak repulsion interaction between the donor and acceptor units and the S N secondary interactions make the dyes to adopt a co-planar molecular conformation and display a peak absorption >880 nm in solution. Importantly, BSFX-BBT can form a desiring J-aggregate in the condensed state, and femtosecond transient absorption spectra reveal that the excited states of J-aggregate are the radiative states, and J-aggregate can facilitate stimulated emission. Consequently, the J-aggregated nanoparticles (NPs) display a peak emission at 1124 nm with a high relative quantum yield of 0.81%. The efficient NIR-II emission, good photothermal effect, and biocompatibility make the J-aggregated NPs demonstrate efficient antitumor efficacy via fluorescence/photoacoustic imaging-guided phototherapy. The paradigm illustrates that tuning the aggregate states of NIR-II dye via spiro-functionalized strategy is an effective approach to enhance photo-theranostic performance.
ABSTRACT
Phototherapy, also known as photobiological therapy, is a non-invasive and highly effective physical treatment method. Its broad use in clinics has led to significant therapeutic results. Phototherapy parameters, such as intensity, wavelength, and duration, can be adjusted to create specific therapeutic effects for various medical conditions. Meanwhile, Magnetic Resonance Imaging (MRI), with its diverse imaging sequences and excellent soft-tissue contrast, provides a valuable tool to understand the therapeutic effects and mechanisms of phototherapy. This review explores the clinical applications of commonly used phototherapy techniques, gives a brief overview of how phototherapy impacts different diseases, and examines MRI's role in various phototherapeutic scenarios. We argue that MRI is crucial for precise targeting, treatment monitoring, and prognosis assessment in phototherapy. Future research and applications will focus on personalized diagnosis and monitoring of phototherapy, expanding its applications in treatment and exploring multimodal imaging technology to enhance diagnostic and therapeutic precision and effectiveness.
Subject(s)
Magnetic Resonance Imaging , Phototherapy , Humans , Magnetic Resonance Imaging/methods , Phototherapy/methods , Treatment OutcomeABSTRACT
Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.
Subject(s)
Copper , Hyaluronic Acid , Magnetic Resonance Imaging , Manganese Compounds , Oxides , Photochemotherapy , Tumor Microenvironment , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Tumor Microenvironment/drug effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Oxides/chemistry , Oxides/pharmacology , Humans , Copper/chemistry , Copper/pharmacology , Particle Size , Nanostructures/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Phototherapy , Nanoparticles/chemistry , Cell Survival/drug effects , Surface Properties , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Drug Screening Assays, Antitumor , AnimalsABSTRACT
Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.
ABSTRACT
We describe a case of Neuromyelitis Optica Spectrum Disorder (NMOSD) mimicking Wernicke's Encephalopathy (WE) to highlight an atypical presentation of NMOSD. A 39-year-old female presented with subacute encephalopathy and progressive ophthalmoplegia. Her MRI revealed T2 hyperintensities involving the mammillary bodies, periaqueductal grey matter, medial thalami, third ventricle, and area postrema. Whole blood thiamine levels were elevated and she did not improve with IV thiamine. CSF was notable for lymphocytic pleocytosis and elevated protein. She tested positive for serum Aquaporin-4 (AQP4) antibody. Subsequent imaging revealed multilevel lesions in the cervical and thoracic spinal cord. Her CSF GFAP antibody also came back positive. She steadily and significantly improved after high-dose IV steroids and plasmapheresis. She later started on chronic rituximab therapy. This represents a unique case of NMOSD presenting with the classical clinical and imaging features of WE, as opposed to the typical presenting symptoms of NMOSD. As such, demyelinating disorders should be considered when there is concern for diencephalic and midline pathologies, particularly without classic WE risk factors. Conversely, clinicians should be aware of secondary nutritional complications arising from severe area postrema syndrome.
ABSTRACT
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1 and is characterized by parathyroid, pancreatic islet, and anterior pituitary tumors. Primary hyperparathyroidism is the most characteristic finding in MEN1, and intraoperative identification and accurate removal of the diseased parathyroid glands are vital since incomplete excision results in recurrence. This case report describes a 59-year-old woman who had pancreatic islet cell tumors and pituitary tumors and underwent selective transsphenoidal adenomectomy. Based on her medical history and examination, the diagnosis of primary hyperparathyroidism in MEN1 was made, and she underwent total parathyroidectomy with autotransplantation with SPY-Elite®ï¸ Fluorescence Imaging (Stryker Corp., Kalamazoo, MI). Intraoperative identification of the parathyroid glands using autofluorescence with real-time intrinsic near-infrared (NIR) imaging made it easier to detect all of the parathyroid hyperplasia. After the surgery, she had hypoparathyroidism and continued with her oral calcium and vitamin D supplementation to maintain normal calcium levels during follow-up. Herein, we would like to advocate that the use of parathyroid gland autofluorescence with real-time intrinsic NIR imaging may be useful for identifying parathyroid tumors in patients with primary hyperparathyroidism in MEN1.
ABSTRACT
Studies of the development and asymmetry of the corpus striatum and thalamus in early childhood are rare. Studies investigating these structures across the lifespan have not presented their changes during childhood and adolescence in detail. For these reasons, this study investigated the effect of age and sex factors on the development and asymmetry of the corpus striatum and thalamus in the 1-18 age group. In this retrospective study, we included 652 individuals [362 (56%) males] aged 1-18 years with normal brain MRI between 2012 and 2021. Absolute and relative volumes of the corpus striatum and thalamus were obtained by segmentation of three-dimensional T1-weighted MRIs with volBrain1.0. We created age-specific volume data and month-based development models with the help of SPSS (ver.28). The corpus striatum and thalamus had cubic absolute volumetric developmental models. The relative volume of the caudate and thalamus (only males) is consistent with the decreasing "growth" model, the others with the decreasing cubic model. The absolute volumes of the males' bilateral corpus striatum and thalamus and the relative volumes of the caudate and thalamus of the females were significantly larger (P < 0.05). The caudate showed right > left lateralization; putamen, globus pallidus, and thalamus showed left > right lateralization.
Subject(s)
Corpus Striatum , Thalamus , Child, Preschool , Adolescent , Female , Male , Humans , Infant , Child , Retrospective Studies , Corpus Striatum/diagnostic imaging , Thalamus/diagnostic imaging , Putamen , Magnetic Resonance ImagingABSTRACT
BACKGROUND: Increased time to diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify whether opportunities to expedite the diagnosis of sarcoma in general practice exist. AIM: To examine pre-diagnostic GP clinical activity before sarcoma diagnosis. DESIGN AND SETTING: An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database [ACCORD]) linked to two primary care datasets (Patron and MedicineInsight). METHOD: The frequency of general practice healthcare utilisation events (general practice attendances, prescriptions, blood test, and imaging requests) were compared in 377 patients with soft tissue sarcoma (STS) and 64 patients with bone sarcoma (BS) in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use started to increase from baseline. RESULTS: In the 6 months pre-diagnosis, patients with sarcoma had a median of 3-4 general practice attendances, around one-third had a GP imaging request (33% [n = 21] BS and 36% [n = 134] STS), and approximately one in five had multiple imaging requests (19% [n = 12] BS and 21% [n = 80] STS). GP imaging requests progressively increased up to eight-fold from 6 months before sarcoma diagnosis (IRR 8.43, 95% confidence interval [CI] = 3.92 to 18.15, P<0.001) and general practice attendances increased from 3 months pre-diagnosis. CONCLUSION: Patients with sarcoma have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes.
Subject(s)
General Practice , Sarcoma , Humans , Sarcoma/diagnosis , Sarcoma/epidemiology , General Practice/statistics & numerical data , Retrospective Studies , Australia/epidemiology , Female , Male , Middle Aged , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/epidemiology , Adult , Bone Neoplasms/diagnosis , Bone Neoplasms/epidemiology , Referral and Consultation/statistics & numerical data , Aged , Registries , Practice Patterns, Physicians'/statistics & numerical data , Early Detection of Cancer/statistics & numerical dataABSTRACT
Introduction: Hyperbaric oxygen treatment (HBOT) remains a recognised treatment for acute carbon monoxide (CO) poisoning, but the utility of HBOT in treating CO-induced delayed neurological sequelae (DNS) is not yet established. Case description: A 26-year old woman presented with reduced consciousness secondary to CO exposure from burning charcoal. She underwent a single session of HBOT with US Navy Treatment Table 5 within six hours of presentation, with full neurological recovery. Eight weeks later, she represented with progressive, debilitating neurological symptoms mimicking Parkinsonism. Magnetic resonance imaging of her brain demonstrated changes consistent with hypoxic ischaemic encephalopathy. The patient underwent 20 sessions of HBOT at 203 kPa (2 atmospheres absolute) for 115 minutes, and received intravenous methylprednisolone 1 g per day for three days. The patient's neurological symptoms completely resolved, and she returned to full-time professional work with no further recurrence. Discussion: Delayed neurological sequelae is a well-described complication of CO poisoning. In this case, the patient's debilitating neurocognitive symptoms resolved following HBOT. Existing literature on treatment of CO-induced DNS with HBOT consists mainly of small-scale studies and case reports, many of which similarly suggest that HBOT is effective in treating this complication. However, a large, randomised trial is required to adequately determine the effectiveness of HBOT in the treatment of CO-induced DNS, and an optimal treatment protocol.
Subject(s)
Carbon Monoxide Poisoning , Hyperbaric Oxygenation , Humans , Female , Adult , Hyperbaric Oxygenation/methods , Carbon Monoxide , Oxygen , Carbon Monoxide Poisoning/complications , Carbon Monoxide Poisoning/therapy , Carbon Monoxide Poisoning/diagnosis , BrainABSTRACT
Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine and myelin synthesis, brain iron concentration may be of primary interest in the investigation of iron dysregulation in ADHD. This study reviewed current evidence of brain iron abnormalities in children and adolescents with ADHD using magnetic resonance imaging methods, such as relaxometry and quantitative susceptibility mapping, to assess brain iron estimates. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed for studies published between January 1, 2008 and July 7, 2023 in Medline, Scopus and Proquest. Regions of interest, brain iron index values and phenotypical information were extracted from the relevant studies. Risk of bias was assessed using a modified version of the National Heart, Lung, and Blood Institute quality assessment tool. Seven cross-sectional studies comparing brain iron estimates in children with ADHD with neurotypical children were included. Significantly reduced brain iron content in medication-naïve children with ADHD was a consistent finding. Two studies found psychostimulant use may increase and normalize brain iron concentration in children with ADHD. The findings were consistent across the studies despite differing methodologies and may lay the early foundation for the recognition of a potential biomarker in ADHD, although longitudinal prospective neuroimaging studies using larger sample sizes are required. Lastly, the effects of iron supplementation on brain iron concentration in children with ADHD need to be elucidated.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Brain , Iron , Neuroimaging , Humans , Attention Deficit Disorder with Hyperactivity/metabolism , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Child , Iron/metabolism , Brain/diagnostic imaging , Brain/metabolism , Adolescent , Magnetic Resonance ImagingABSTRACT
The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092â nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5â mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.
Subject(s)
Cyclobutanes , Nanoparticles , Neoplasms , Photoacoustic Techniques , Humans , Nanoparticles/therapeutic use , Theranostic Nanomedicine/methods , Phenols/pharmacology , Cyclobutanes/pharmacology , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Phototherapy , Photoacoustic Techniques/methods , Cell Line, TumorABSTRACT
Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.
Subject(s)
Magnetic Resonance Imaging , Mindfulness , Obsessive-Compulsive Disorder , Humans , Obsessive-Compulsive Disorder/therapy , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/physiopathology , Male , Female , Adult , Mindfulness/methods , Rest/physiology , Brain/diagnostic imaging , Brain/physiopathology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Young Adult , Middle Aged , Cognitive Behavioral Therapy/methods , Default Mode Network/diagnostic imaging , Default Mode Network/physiopathology , Treatment Outcome , Neural Pathways/physiopathology , Neural Pathways/diagnostic imagingABSTRACT
Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g-1 cm-1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.
Subject(s)
Germanium , Photoacoustic Techniques , Phototherapy , Animals , Mice , Photoacoustic Techniques/methods , Germanium/chemistry , Phototherapy/methods , Disease Models, Animal , Lasers , Nanoparticles/chemistry , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Biocompatible Materials/chemistry , Cell Line, Tumor , Neoplasms/therapy , Neoplasms/diagnostic imaging , FemaleABSTRACT
Human neural progenitor cells (hNPCs) hold promise for treating spinal cord injury. Studies to date have focused on improving their regenerative potential and therapeutic effect. Equally important is ensuring successful delivery and engraftment of hNPCs at the injury site. Unfortunately, no current imaging solution for cell tracking is compatible with long-term monitoring in vivo. The objective of this study was to apply a novel bright-ferritin magnetic resonance imaging (MRI) mechanism to track hNPC transplants longitudinally and on demand in the rat spinal cord. We genetically modified hNPCs to stably overexpress human ferritin. Ferritin-overexpressing (FT) hNPCs labeled with 0.2 mM manganese provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, morphology, proliferation, and differentiation. In vivo, 2 M cells were injected into the cervical spinal cord of Rowett nude rats. MRI employed T1-weighted acquisitions and T1 mapping on a 3 T scanner. Conventional short-term cell tracking was performed using exogenous Mn labeling prior to cell transplantation, which displayed transient bright contrast on MRI 1 day after cell transplantation and disappeared after 1 week. In contrast, long-term cell tracking using bright-ferritin allowed on-demand signal recall upon Mn supplementation and precise visualization of the surviving hNPC graft. In fact, this new cell tracking technology identified 7 weeks post-transplantation as the timepoint by which substantial hNPC integration occurred. Spatial distribution of hNPCs on MRI matched that on histology. In summary, bright-ferritin provides the first demonstration of long-term, on-demand, high-resolution, and specific tracking of hNPCs in the rat spinal cord.
Subject(s)
Cell Tracking , Ferritins , Magnetic Resonance Imaging , Neural Stem Cells , Rats, Nude , Spinal Cord , Animals , Magnetic Resonance Imaging/methods , Neural Stem Cells/cytology , Neural Stem Cells/transplantation , Neural Stem Cells/metabolism , Cell Tracking/methods , Humans , Rats , Ferritins/metabolism , Spinal Cord/metabolism , Spinal Cord/diagnostic imaging , Stem Cell Transplantation/methods , Cell Differentiation , Spinal Cord Injuries/therapyABSTRACT
In Robo3cKO mice, midline crossing defects of the trigeminothalamic projections from the trigeminal principal sensory nucleus result in bilateral whisker maps in the somatosensory thalamus and consequently in the face representation area of the primary somatosensory (S1) cortex (Renier et al., 2017; Tsytsarev et al., 2017). We investigated whether this bilateral sensory representation in the whisker-barrel cortex is also reflected in the downstream projections from the S1 to the primary motor (M1) cortex. To label these projections, we injected anterograde viral axonal tracer in S1 cortex. Corticocortical projections from the S1 distribute to similar areas across the ipsilateral hemisphere in control and Robo3cKO mice. Namely, in both genotypes they extend to the M1, premotor/prefrontal cortex (PMPF), secondary somatosensory (S2) cortex. Next, we performed voltage-sensitive dye imaging (VSDi) in the left hemisphere following ipsilateral and contralateral single whisker stimulation. While controls showed only activation in the contralateral whisker barrel cortex and M1 cortex, the Robo3cKO mouse left hemisphere was activated bilaterally in both the barrel cortex and the M1 cortex. We conclude that the midline crossing defect of the trigeminothalamic projections leads to bilateral whisker representations not only in the thalamus and the S1 cortex but also downstream from the S1, in the M1 cortex.
Subject(s)
Motor Cortex , Somatosensory Cortex , Mice , Animals , Somatosensory Cortex/physiology , Vibrissae/physiology , Motor Cortex/physiology , Thalamus/diagnostic imaging , Trigeminal NucleiABSTRACT
OBJECTIVE: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. METHODS: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. RESULTS: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. CONCLUSION: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level.
Subject(s)
Acupuncture Therapy , Cognitive Dysfunction , Hippocampus , Magnetic Resonance Imaging , Humans , Hippocampus/diagnostic imaging , Hippocampus/pathology , Hippocampus/physiopathology , Acupuncture Therapy/methods , Male , Female , Cognitive Dysfunction/therapy , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Aged , Neuropsychological Tests , White Matter/diagnostic imaging , White Matter/pathology , Middle AgedABSTRACT
PURPOSE: To investigate the differences in baseline staging of anal squamous cell carcinoma based on CT, MRI, and PET/CT, and the resultant impact on the radiation plan. METHODS: This retrospective study included consecutive patients with anal squamous cell carcinoma who underwent baseline pelvic MRI, CT, and PET/CT (all examinations within 3 weeks of each other) from January 2010 to April 2020. CTs, MRIs, and PET/CTs were re-interpreted by three separate radiologists. Several imaging features were assessed; tumor stage was determined based on the eight edition of the American Joint Committee on Cancer (AJCC) staging manual; and T (tumor), N (node), and M (metastasis) categories were determined based on National Comprehensive Cancer Network (NCCN) guidelines. Radiologist assessments were then randomly presented to a radiation oncologist who formulated the radiation plan in a blinded fashion. RESULTS: Across 28 patients (median age, 62 years [range, 31-78], T-category classification was significantly different on PET/CT compared to MRI and CT (p = 0.037 and 0.031, respectively). PET/CT staged a higher proportion of patients with T1/T2 disease (16/28, 57%) compared to MRI (11/28, 39%) and CT (10/28, 36%). MRI staged a higher proportion of patients with T3/T4 disease (14/28, 50%) compared to CT (12/28, 43%) and PET/CT (11/28, 39%). However, there was no significant difference between the three imaging modalities in terms of either N-category, AJCC staging, or NCCN TNM group classification, or in treatment planning. CONCLUSION: Our exploratory study showed that MRI demonstrated a higher proportion of T3/T4 tumors, while PET/CT demonstrated more T1/T2 tumors; however, MRI, CT, and PET/CT did not show any significant differences in AJCC and TNM group categories, nor was there any significant difference in treatment doses between them when assessed independently by an experienced radiation oncologist.
Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , Magnetic Resonance Imaging , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Tomography, X-Ray Computed , Humans , Positron Emission Tomography Computed Tomography/methods , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/radiotherapy , Anus Neoplasms/pathology , Female , Male , Middle Aged , Magnetic Resonance Imaging/methods , Retrospective Studies , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/pathology , Adult , Tomography, X-Ray Computed/methods , Radiotherapy Planning, Computer-Assisted/methodsABSTRACT
Sonodynamic therapy (SDT) utilizes ultrasonic excitation of a sensitizer to generate reactive oxygen species (ROS) to destroy tumor. Two dimensional (2D) black phosphorus (BP) is an emerging sonosensitizer that can promote ROS production to be used in SDT but it alone lacks active targeting effect and showed low therapy efficiency. In this study, a stable dispersion of integrated micro-nanoplatform consisting of BP nanosheets loaded and Fe3O4 nanoparticles (NPs) connected microbubbles was introduced for ultrasound imaging guided and magnetic field directed precision SDT of breast cancer. The targeted ultrasound imaging at 18 MHz and efficient SDT effects at 1 MHz were demonstrated both in-vitro and in-vivo on the breast cancer. The magnetic microbubbles targeted deliver BP nanosheets to the tumor site under magnetic navigation and increased the uptake of BP nanosheets by inducing cavitation effect for increased cell membrane permeability via ultrasound targeted microbubble destruction (UTMD). The mechanism of SDT by magnetic black phosphorus microbubbles was proposed to be originated from the ROS triggered mitochondria mediated apoptosis by up-regulating the pro-apoptotic proteins while down-regulating the anti-apoptotic proteins. In conclusion, the ultrasound theranostic was realized via the magnetic black phosphorus microbubbles, which could realize targeting and catalytic sonodynamic therapy.