Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities

Transkraniaalne aju ultraheliuuring Eesti parkinsoni tõve haigetel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneEestis läbiviidud uurimustöö eesmärgiks oli näidata aju ultraheli uuringu abil Parkinsoni tõve korral tekkivaid muutusi keskajus asuvas musttuumas, mis aitaks seda haigust diagnoosida. Täiendavalt uuriti ka ultraheliuuringu tulemuste seoseid depressiivsete sümptomite esinemisega. Tegemist on innovaatilise meetodiga Parkinsoni tõve diagnoosimiseks, mida Eestis pole varem uuritud. Uuringus osales 300 PT patsienti ja 200 kontrollisikut. Aju musttuum sisaldab dopamiinirakke, mis Parkinsoni tõvega haigetel haiguse kulu jooksul hävinevad. Läbi kolju tehtava ultraheliuuringu käigus on võimalik mõõta musttuuma piirkonna suurust ja selle kajarikkuse (hüperehhogeensuse) asümmeetria alusel kinnitada Parkinsoni tõve diagnoosi. Uuringul määrati ultraheli diagnostiline väärtus haigete eristamiseks tervetest, mis ühtib varasemalt teistes riikides leitud tulemustega; kõige olulisemaks tulemuse mõjutajaks on vanus. Lisaks näidati erinevust vasaku ja parema ajupoole vahel, mis on seoses esmassümptomite tekkimise poolega. Lisaks aitab ultraheliuuring kirjeldada depressiivsete sümptomite ilmnemist Parkinsoni tõvega haigetel ajutüves asuvate Raphe tuumade ehhogeensuse esinemise põhjal. Raphe tuumad osalevad virgatsaine serotoniini tootmisel, mille vähenemisel kahjustuse korral võivad tekkida depressiooni sümptomid. Uuring näitas, et ultraheli uuring võimaldab hinnata Raphe tuumade terviklikkust ja on hea meetod varjatud depressiooni sümptomite väljaselgitamiseks. Läbiviidud uuring oli esimene ulatuslik aju ultraheliuuring Eestis, mis kinnitas ultraheliuuringu diagnostilist väärtust Parkinsoni tõve diagnoosimiseks. Lisaks teaduslikule väärtusele on sellel oluline kliiniline tähtsus seoses uue meetodi rakendamisega Parkinsoni tõve käsitluses.The aim of the research carried out in Estonia was to show by transcranial brain sonography the changes in Parkinson's disease in substantia nigra, which would help diagnose the disease. Transcranial brain sonography is an innovative method for diagnosing Parkinson's disease, which has not been studied in Estonia before. By sonography examination of the skull, it is possible to measure the size of the substantia nigra echogenicity and confirm the diagnosis of Parkinson's disease on the basis of its asymmetry in substantia nigra hyperechogenicity. The study determined the diagnostic value of SN+ to distinguish patients from healthy ones, which is consistent with the results previously found in other countries. There was a difference between the left and right sides of the SN+ that are related to the onset of the Parkinson’s disease initial symptoms. In addition, age was the most important factor influencing the asymmetry of SN+. The ultrasound study helps to describe the appearance of depressive symptoms in PD patients based on the occurrence of echogenicity of Raphe nuclei in the brainstem. The study showed that the transcranial brain sonography examination provides an estimate of the integrity of the Raphe nuclei and is a good method for detecting the symptoms of hidden depression. The conducted study was the first extensive transcranial brain sonography study in Estonia confirming the diagnostic value of ultrasound in the diagnosis of Parkinson's disease.  https://www.ester.ee/record=b5250326~S

Ultrasound indices of congestion in patients with acute heart failure according to body mass index

Background: The inverse relationship between body mass index (BMI) and natriuretic peptide levels complicates the diagnosis of heart failure (HF) in obese patients. Assessment of congestion with ultrasound could facilitate HF diagnosis but it is unclear if any relationship exists amongst BMI, inferior vena cava (IVC) diameter and the number of B-lines. Methods: We performed a comprehensive echocardiographic evaluation within 24 h from hospital admission in patients with HF, including lung B-lines and IVC diameter, and studied their relationship with BMI and outcome. Results: 216 patients (median age 81 (77–86) years) were enrolled. Median number of B-lines was 31 (IQR 26–38), median IVC diameter was 23 (22–25) mm and median BNP 991 (727–1601) pg/mL. BMI was inversely correlated with B-lines (r = − 0.50, p < 0.001), but not with IVC diameter (r = − 0.04, p = 0.58). Compared to overweight patients (BMI 25–29.9 kg/m2; n = 100) or with a normal BMI (BMI < 25 kg/m2; n = 59), obese patients (BMI ≥ 30 kg/m2; n = 57) had lower B-lines [28 (24–33) vs 30 (26–35), and vs 38 (32–42), respectively; p < 0.001] but similar IVC diameter. During the first 60 days of follow-up, there were 53 primary events: 29 patients died and 24 had a HF-related hospitalisation. B-lines and IVC diameter were independently associated with an increased risk. However, B-lines were less likely to predict outcome in the subgroup of patients with a BMI ≥ 30 kg/m2. Conclusions: Assessment of IVC diameter or B-lines in patients admitted with AHF identifies those at greater risk of death or HF readmission. However, assessment of B-lines might be influenced by BMI

Non-enhancing gliomas: does intraoperative ultrasonography improve resections?

Purpose Non-enhancing diffuse gliomas are a challenging surgical proposition. Delineation of tumor extent on preoperative imaging and intraoperative visualization are often difficult. Methods We retrospectively analyzed all cases of non-enhancing gliomas that were operated on using navigated 3-dimensional ultrasonography (US). tumor delineation (good, moderate, or poor) on preoperative magnetic resonance imaging (MRI) and intraoperative US was compared. Post-resection US findings with respect to residual tumor status were compared to the postoperative imaging findings. The extent of resection was calculated and recorded. Results There were 55 gliomas (43 high-grade, 12 low-grade). Forty were close to eloquent areas. The pre-resection concordance of MRI with US was 56%, with US defining more tumors as well-delineated (n=26) than MRI (n=13). US was used for resection control in 50 cases. Gross tumor resection was achieved in 24 cases (51%). US correctly predicted the residual tumor status in 78% of cases. The use of US led to radical resections even in some tumors preoperatively deemed to be unresectable. However, eloquent location was the only independent predictor of the extent of resection. Conclusion Intraoperative US is a useful tool for guiding resection of non-enhancing gliomas. It may be better than MRI for delineating these tumors, and may thereby facilitate improved resection of these otherwise poorly delineated tumors. However, functional boundaries remain the main limiting factor for achieving complete resection of non-enhancing gliomas

セツキシマブ被覆アルブミンマイクロバブルと超音波の併用による口腔扁平上皮癌細胞の細胞死滅およびアポトーシスの増強について

福岡大学201

A customized multispectral needle probe combined with a virtual photometric setup for in vivo detection of Lewis lung carcinoma in an animal model

Optical systems applied for tissue analysis are primarily based on single spectroscopic techniques. This paper however presents a multispectral backscattering sensor designed for in vivo application by a specially formed probe tip which allows side by side monitoring of ultraviolet, visible, near-infrared and fluorescence spectra. The practical applicability of the measurement system was demonstrated in vitro (muscle and adipose tissue) and in vivo in an animal model (mouse). By comparing associated measuring changes in biochemical, physical-morphological and colorimetric values this procedure allows a differentiation between healthy, marginal and malignant tissue

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data

Measurement of left ventricular deformation using 3D echocardiography

Bakgrunn: 3D speckle tracking ekkokardiografi (STE) er en hjerteultralydmetode som gir mulighet for måling av deformasjonsparametere, som strain, rotasjon, tvist og torsjon. Den største begrensningen for 3D STE er lav tids- og romlig oppløsning. Økes den ene oppløsingen vil den andre bli redusert. I tillegg vil andre faktorer som antall flettede bilder, sektorstørrelse og dybde påvirke begge oppløsningene. Denne avhandlingen har hatt som mål å finne tilstander og opptaksinnstillinger for å optimalisere nøyaktigheten til 3D STE-parametere i et kontrollert miljø. Videre har det vært som mål å finne regional deformasjon fra 3D STE i en klinisk studie på pasienter med aortaklaffestenose (AS) ved bruk av optimaliserte innstillinger. Materiale og metode: Studie 1 og 2 utforsket nøyaktigheten til 3D STE ved bruk av et in vitro-oppsett med et fantom av venstre ventrikkel. Studie 1 sammenlignet 3D STE strain mot sonomikromertri som gullstandard i longitudinell, sirkumferensiell og radiell retning. Ved å bruke et annet fantom i studie 2 ble 3D STE tvist sammenlignet mot sonomikrometri tvist for å finne nøyaktigheten til 3D STE tvistmålinger. Studie 3 inkluderte 85 pasienter med variabel grad av AS i en tverrsnittstudie. 3D ekkokardiografi ble utført og 3D STE-parametere ble sammenlignet mellom grupper av pasienter med mild, moderat og alvorlig AS. Resultater: Studie 1 fant godt samsvar mellom 3D STE og sonomikrometri med optimalt volum rate på 36,6 volumer per sekund (VPS) ved bruk av 6 sammenflettede bilder. I studie 2 hadde 3D STE godt samsvar ved bruk av både 4 og 6 sammenflettede bilder med volum rater på henholdsvis 20,3 og 17,1 VPS. Studie 3 fant lavere global longitudinal strain i pasienter med alvorlig AS sammenlignet med mild AS. Basal og midtre longitudinal strain var også lavere i alvorlig sammenlignet med mild AS. Apikal-basal ratio var høyere for moderat i forhold til mild AS. Maks apikal-basal tvist var høyere hos pasienter med alvorlig sammenlignet med mild og moderat AS. Konklusjon: Måling av venstre ventrikkelfunksjon med 3D STE er mest nøyaktig med volum rater < 40 VPS. Høy romlig oppløsning virker å være mer viktig enn tidsoppløsning. Pasienter med alvorlig AS har lavere global, basal og midtre longitudinal strain enn pasienter med mild AS, ved bruk av 3D STE. De har også høyere tvist enn mild og moderat AS. Områder som involverer apeks, har høyere spredning av data og har antagelig lavere nøyaktighet ved bruk av 3D STE.Background: 3D speckle tracking echocardiography (STE) enables measurement of multiple parameters of deformation, such as strain, rotation, twist and torsion. The main limitation of 3D STE is low temporal and spatial resolution. Increasing resolution in time will decrease resolution in space, and vice versa. In addition, other factors such as number of stitched images, sector size and depth, influence the resolution. This thesis aimed to find conditions and acquisition settings to optimize accuracy for 3D STE parameters in a controlled in vitro environment. Secondly, it aimed to evaluate regional deformation by 3D STE in a clinical study on patients with aortic valve stenosis (AS) using optimized settings. Materials and methods: Study 1 and 2 explored the accuracy of 3D STE using an in vitro setup with a left ventricle (LV) phantom. Study 1 compared 3D STE strain to strain by sonomicrometry as the gold standard. Measurements were compared in both longitudinal, circumferential and radial direction. Using a different twisting phantom in study 2, 3D STE twist was compared to twist by sonomicrometry to evaluate the accuracy of 3D STE twist. Study 3 was a cross-sectional analysis of 85 patients with variable degree of AS in a cross-sectional study. 3D echocardiography was done, and 3D STE parameters were compared between groups of patients with mild, moderate and severe AS. Results: Study 1 found 3D STE strain to have good agreement with sonomicrometry. Optimal acquisition settings were found to be volume rate 36.6 volumes per second (VPS) obtained by 6 stitched images. Study 2 found 3D STE twist to have good agreement with sonomicrometry when using both 4 and 6 stitched images with volume rates 20.3 and 17.1 VPS, respectively. Study 3 found global longitudinal strain to be lower in patients with severe AS compared to those with mild AS. Basal and mid longitudinal strains were also lower in severe AS than in mild AS. Apical basal ratio was higher for moderate than mild AS. Peak apical-basal twist was higher in patients with severe AS than in those with mild and moderate AS. Conclusion: Assessment of LV function by 3D STE is most accurate at volume rates < 40 VPS. High spatial resolution seems to be more important than temporal resolution. Patients with severe AS have lower global, as well as lower regional basal and mid longitudinal strain compared to patients with mild AS, assessed with 3D STE. They also have higher twist than mild and moderate AS. Segments involving the apex have high dispersion and probably lower accuracy in 3D STE.Doktorgradsavhandlin