scholarly journals Iron Nanoparticles as Magnetic Resonance Imaging Contrast Agents

2021 ◽  
Author(s):  
◽  
Peter Maurer Ferguson
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Magnetic Nanoparticles ◽  
Lymph Nodes ◽  
Contrast Agents ◽  
Iron Nanoparticles ◽  
Mri Contrast ◽  
Lymph Node Size ◽  
Node Size

<p>Magnetic nanoparticles are effective in a range of biomedical applications including magneticresonance imaging (MRI) contrast enhancement. The efficacy of nanoparticles ascontrast agents depends mainly on the surface chemistry and magnetic properties of theparticles, with a large magnetic moment inducing efficient transverse (T₂) relaxation ofprotons. This results in improved negative enhancement of MRI contrast on T₂ weightedsequences. Iron oxide nanoparticles (FeOx NPs) have been used in MRI for 20 years andare the only commercially available T₂ contrast agents. A significantly larger magneticmoment can potentially be achieved with iron nanoparticles (Fe NPs), but developmenthas been hampered by difficulty in preparing stable particles. In this study, stable Fe NPwere prepared by a novel, simple, synthesis and compared with FeOx NP as T₂ contrastagents in a range of MRI-based biomedical applications.The effectiveness of Fe NPs versus FeOx NPs to negatively enhance MRI contrast onT₂ weighted sequences was first examined in vitro. The Fe NPs and FeOx NPs werecharacterised by electron microscopy and found to be of similar size (16nm). The Fe NPspossessed a core of highly magnetic α-Fe inside a 3nm shell of FeOx of the same crystalstructure as the pure FeOx NPs. Both types of NP were coated with the same molecule,DMSA, to produce aqueous dispersions with similar hydrodynamic particle sizes andpharmacokinetics. When dispersed in gels and examined by MRI, the Fe NPs were foundto produce more than twice the amount of T₂ contrast change per unit concentrationrelative to FeOx NPs. When cells were labelled in vitro, Fe NPs produced greater T₂contrast enhancement in all cell types tested, whilst there was no significant difference in the uptake of iron or the cytotoxicity between cells labelled with Fe or FeOx NPs.To assess the clinical applicability of the nanoparticles in vivo, FeOx NPs and Fe NPswere administered to mice and MRI experiments were performed at 1.5 T. Contrast effectsof the NPs were examined in the liver, spleen and lymph nodes, as tissues in theseorgans are rich in phagocytic cells and have a strong tendency to take up circulatingNPs. In all three organs studied, the Fe NPs produced noticeably darker contrast thanthe FeOx NPs, providing twice the contrast improvement.One of the most intensely researched applications of magnetic nanoparticles in MRI is improving detection of cancer in the lymph nodes. To model the size and NP uptake ofsmall lymph node metastases in humans, a mouse model was developed by injecting 4T1breast cancer cells directly into the mouse spleen. Analysis of mice bearing 4T1 tumoursperformed at 1.5 T showed that Fe NPs produced better contrast than FeOx NPs andimproved the detection of small tumours in the spleen as determined by two blindedradiologists. Indeed, the heightened sensitivity and specificity improved the threshold ofcancer detection on previous studies performed at 1.5 T.It was then examined whether the improved T₂ contrast could enable new MRI applicationsin vivo. A novel assay to detect induced immune responses following dendriticcell-based vaccination using MRI was developed. By tracking cells labelled with ironnanoparticles, a difference in contrast could be detected between nave mice and thosethat had developed a strong immune response after vaccination. This assay only reachedstatistical significance with Fe NPs and not with FeOx NPs.As a consequence of these studies, another MRI-based technique for assessing inductionof an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged. This enlargement was seen as early as 12 hours after vaccination and was caused by a cellular in filtrate dominated by lymphoidcells. In experiments where vaccination was performed multiple times using different tumoursas a source of antigen, incremental increases in lymph node size were detectableby MRI, which was shown to be a highly antigen-specific response. In the vaccine modelstudied, the increase in lymph node size was associated with protection from a tumour challenge. Thus, Fe NPs produce a significant improvement of T₂ contrast over FeOx NPs in a rangeof applications without any differences found in uptake or cytotoxicity. These findingsare substantial enough to justify further investigations into the application of Fe NPs ina variety of clinical settings.</p>

scholarly journals Iron Nanoparticles as Magnetic Resonance Imaging Contrast Agents

2021 ◽  
Author(s):  
◽  
Peter Maurer Ferguson
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Magnetic Nanoparticles ◽  
Lymph Nodes ◽  
Contrast Agents ◽  
Iron Nanoparticles ◽  
Mri Contrast ◽  
Lymph Node Size ◽  
Node Size

<p>Magnetic nanoparticles are effective in a range of biomedical applications including magneticresonance imaging (MRI) contrast enhancement. The efficacy of nanoparticles ascontrast agents depends mainly on the surface chemistry and magnetic properties of theparticles, with a large magnetic moment inducing efficient transverse (T₂) relaxation ofprotons. This results in improved negative enhancement of MRI contrast on T₂ weightedsequences. Iron oxide nanoparticles (FeOx NPs) have been used in MRI for 20 years andare the only commercially available T₂ contrast agents. A significantly larger magneticmoment can potentially be achieved with iron nanoparticles (Fe NPs), but developmenthas been hampered by difficulty in preparing stable particles. In this study, stable Fe NPwere prepared by a novel, simple, synthesis and compared with FeOx NP as T₂ contrastagents in a range of MRI-based biomedical applications.The effectiveness of Fe NPs versus FeOx NPs to negatively enhance MRI contrast onT₂ weighted sequences was first examined in vitro. The Fe NPs and FeOx NPs werecharacterised by electron microscopy and found to be of similar size (16nm). The Fe NPspossessed a core of highly magnetic α-Fe inside a 3nm shell of FeOx of the same crystalstructure as the pure FeOx NPs. Both types of NP were coated with the same molecule,DMSA, to produce aqueous dispersions with similar hydrodynamic particle sizes andpharmacokinetics. When dispersed in gels and examined by MRI, the Fe NPs were foundto produce more than twice the amount of T₂ contrast change per unit concentrationrelative to FeOx NPs. When cells were labelled in vitro, Fe NPs produced greater T₂contrast enhancement in all cell types tested, whilst there was no significant difference in the uptake of iron or the cytotoxicity between cells labelled with Fe or FeOx NPs.To assess the clinical applicability of the nanoparticles in vivo, FeOx NPs and Fe NPswere administered to mice and MRI experiments were performed at 1.5 T. Contrast effectsof the NPs were examined in the liver, spleen and lymph nodes, as tissues in theseorgans are rich in phagocytic cells and have a strong tendency to take up circulatingNPs. In all three organs studied, the Fe NPs produced noticeably darker contrast thanthe FeOx NPs, providing twice the contrast improvement.One of the most intensely researched applications of magnetic nanoparticles in MRI is improving detection of cancer in the lymph nodes. To model the size and NP uptake ofsmall lymph node metastases in humans, a mouse model was developed by injecting 4T1breast cancer cells directly into the mouse spleen. Analysis of mice bearing 4T1 tumoursperformed at 1.5 T showed that Fe NPs produced better contrast than FeOx NPs andimproved the detection of small tumours in the spleen as determined by two blindedradiologists. Indeed, the heightened sensitivity and specificity improved the threshold ofcancer detection on previous studies performed at 1.5 T.It was then examined whether the improved T₂ contrast could enable new MRI applicationsin vivo. A novel assay to detect induced immune responses following dendriticcell-based vaccination using MRI was developed. By tracking cells labelled with ironnanoparticles, a difference in contrast could be detected between nave mice and thosethat had developed a strong immune response after vaccination. This assay only reachedstatistical significance with Fe NPs and not with FeOx NPs.As a consequence of these studies, another MRI-based technique for assessing inductionof an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged. This enlargement was seen as early as 12 hours after vaccination and was caused by a cellular in filtrate dominated by lymphoidcells. In experiments where vaccination was performed multiple times using different tumoursas a source of antigen, incremental increases in lymph node size were detectableby MRI, which was shown to be a highly antigen-specific response. In the vaccine modelstudied, the increase in lymph node size was associated with protection from a tumour challenge. Thus, Fe NPs produce a significant improvement of T₂ contrast over FeOx NPs in a rangeof applications without any differences found in uptake or cytotoxicity. These findingsare substantial enough to justify further investigations into the application of Fe NPs ina variety of clinical settings.</p>

scholarly journals Omental Vascularized Lymph Node Flap: A Radiographic Analysis

2018 ◽  
Vol 34 (07) ◽  
pp. 472-477 ◽  
Author(s):  
Sarah Sasor ◽  
Sunil Tholpady ◽  
Michael Chu ◽  
Julia Cook
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Donor Site ◽  
Gaussian Mixture ◽  
Omental Flap ◽  
Node Number ◽  
Lymph Node Size ◽  
Lymph Node Transfer ◽  
Node Size ◽  
Vascularized Lymph Node Transfer

Background Vascularized lymph node transfer is an increasingly popular option for the treatment of lymphedema. The omental donor site is advantageous for its copious soft tissue, well-defined collateral circulation, and large number of available nodes, without the risk of iatrogenic lymphedema. The purpose of this study is to define the anatomy of the omental flap in the context of vascularized lymph node harvest. Methods Consecutive abdominal computed tomography angiography (CTA) images performed at a single institution over a 1-year period were reviewed. Right gastroepiploic artery (RGEA) length, artery caliber, lymph node size, and lymph node location in relation to the artery were recorded. A two-tailed Z-test was used to compare means. A Gaussian Mixture Model confirmed by normalized entropy criterion was used to calculate three-dimensional lymph node cluster locations along the RGEA. Results In total, 156 CTA images met inclusion criteria. The RGEA caliber at its origin was significantly larger in males compared with females (p < 0.001). An average of 3.1 (1.7) lymph nodes were present per patient. There was no significant gender difference in the number of lymph nodes identified. Average lymph node size was significantly larger in males (4.9 [1.9] × 3.3 [0.6] mm in males vs. 4.5 [1.5] × 3.1 [0.5] mm in females; p < 0.001). Three distinct anatomical variations of the RGEA course were noted, each with a distinct lymph node clustering pattern. Total lymph node number and size did not differ among anatomical subgroups. Conclusion The omentum is a reliable lymph node donor site with consistent anatomy. This study serves as an aid in preoperative planning for vascularized lymph node transfer using the omental flap.

Ultrasonographic, endoscopic and histological appearances of the caecum in cats presenting with chronic clinical signs of caecocolic disease

2016 ◽  
Vol 19 (2) ◽  
pp. 94-104 ◽  
Author(s):  
Harriet Hahn ◽  
Pascaline Pey ◽  
Aurélie Baril ◽  
Julie Charpentier ◽  
Loic Desquilbet ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Clinical Signs ◽  
Wall Thickening ◽  
Abdominal Ultrasonography ◽  
Tissue Samples ◽  
Mesenteric Fat ◽  
Lymph Node Size ◽  
Histological Characteristics ◽  
Node Size

Objectives This study aimed to describe the ultrasonographic, endoscopic and histological characteristics of the caecum and ileocaecocolic junction in cats suffering from chronic clinical signs compatible with caecocolic disease. Methods Cats presenting with clinical signs suggestive of a caecocolic disease were prospectively recruited. All cats underwent an ultrasonographic examination of the caecum, ileum, colon, ileocolic lymph nodes and local mesenteric fat, in addition to comprehensive abdominal ultrasonography. This was followed by a colonoscopy with a macroscopic assessment of the caecocolic mucosa; caecocolic tissue samples were systematically collected for histologic analysis. Results Eighteen cats were included. Eleven of 18 cats had ultrasonographic abnormalities adjacent to the ileocaecocolic junction (lymphadenopathy, local steatitis) and 13/18 cats had abnormalities directly related to the junction (wall thickening, loss of wall layering). Seventeen of 18 cats had at least one ultrasonographic abnormality. Endoscopically, hyperaemia, oedema, discoloration and/or erosions were found in all cats. Each cat was classified as having mild or moderate-to-severe lesions according to endoscopic results; no classification could be established statistically for ultrasonographic results. The accentuation of the dimpled pattern tended to be inversely related to the severity of endoscopic lesion scoring. Histologically, a large proportion of cats showed typhlitis (13/16), one had lymphoma and two were normal. All cats with typhlitis also had colitis. There was only slight agreement between endoscopic and histological caecal results regarding the severity of lesions. Loss of caecal wall layering on ultrasound was found in 7/18 cats and, surprisingly, did not appear as a reliable predictor of the severity of inflammation or of malignancy; neither did local steatitis nor lymph node size. Conclusions and relevance Ultrasonography and endoscopy should not be used as the sole methods to investigate the ileocaecocolic region in cats with clinical signs suggestive of caecocolic disease. The presence of chronic clinical signs should routinely prompt histological biopsy.

Determinants of False-Negative Fine-Needle Aspirates of Axillary Lymph Nodes in Women with Breast Cancer: Lymph Node Size, Cortical Thickness and Hilar Fat Retention

2015 ◽  
Vol 59 (4) ◽  
pp. 311-314 ◽  
Author(s):  
D. Eric Ewing ◽  
Lester J. Layfield ◽  
Christopher L. Joshi ◽  
Mark D. Travis
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Cortical Thickness ◽  
False Negative ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
True Positive ◽  
False Negatives ◽  
Lymph Node Size ◽  
Node Size

Objective: Ultrasound-guided fine-needle aspiration (UG-FNA) is utilized to sample axillary lymph nodes in breast cancer patients. Diagnostic sensitivity is good but few data exist regarding the causes of false-negative results. Study Design: Fifty-four UG-FNAs of sentinel lymph nodes with histologic follow-up were identified. Gross and radiographic lymph node size, the percentage replaced by carcinoma and the cortical thickness were correlated with false-negative rates. Results: Thirty-seven aspirates were negative, 5 of these being false-negative (9%). True-positive lymph nodes averaged 1.3 cm in dimension while false-negatives averaged 0.92 cm. Percentage involvement by carcinoma for true-positive FNAs averaged 69% while false-negatives averaged 25%. Cortical thickness averaged 5.6 mm in true-positive FNAs but 2.9 mm in false-negatives. Conclusion: A relationship exists between lymph node size and the likelihood of a false-negative FNA. Lymph nodes <1.2 cm have a higher incidence of false-negative results. Lymph nodes with <30% involvement demonstrated a higher percentage of false-negatives than those with >30% replacement. Sentinel lymph nodes <1 cm appear to be relatively poor candidates for UG-FNA. Lymph nodes with a cortical thickness <3.5 mm are more often associated with a false-negative result than nodes with a thicker cortex.

scholarly journals Genetic encoding of targeted MRI contrast agents for in vivo tumor imaging

2019 ◽  
Author(s):  
Simone Schuerle ◽  
Maiko Furubayashi ◽  
Ava P. Soleimany ◽  
Tinotenda Gwisai ◽  
Wei Huang ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Contrast Agents ◽  
Tumor Imaging ◽  
Mri Contrast Agents ◽  
Contrast Effects ◽  
Mri Contrast ◽  
Magnetic Resonance Imaging Mri ◽  
Targeted Mri

AbstractTumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with transgenic targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically-encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic αv integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.

scholarly journals A retrospective study of endobronchial ultrasound transbronchial needle aspiration versus conventional transbronchial needle aspiration in diagnosis/staging of hilar/mediastinal lymph node in lung cancer: Which role in clinical practice?

2019 ◽  
Vol 89 (1) ◽  
Author(s):  
Sergio C. Conte ◽  
Giulia Spagnol ◽  
Marco Biolo ◽  
Marco Confalonieri
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Diagnostic Accuracy ◽  
Mediastinal Lymph Node ◽  
Needle Aspiration ◽  
Endobronchial Ultrasound ◽  
First Choice ◽  
Lymph Node Size ◽  
Node Size

The conventional-trans bronchial needle aspiration (c-TBNA) has been the first procedure for sampling hilar/mediastinal lymph node for the diagnosis/staging of lung cancer. In the last decade the endobronchial ultrasound trans bronchial needle aspiration (EBUS-TBNA) was introduced in clinical practice and became the first-choice exam in diagnosis and staging of lung cancer. The aim of this study was to compare the diagnostic accuracy (DA), sensitivity and adequacy of c-TBNA and EBUS-TBNA. It was a retrospective and observational multicenter study. The first endpoint was diagnostic accuracy of EBUS-TBNA versus c-TBNA. The secondary end-points were sensitivity and adequacy. Two hundred and nine consecutive patients underwent the procedure, 99 EBUS-TBNA and 110 c-TBNA. When lymph nodes with short axis <2 cm the diagnostic accuracy for correct diagnosis was 94.2% in EBUS-TBNA group and 89.7% in c-TBNA group (p=0.01); the sample adequacy was 70.3% and 42%, respectively (p=0.01); the sensitivity was 93% (95% CI, 82-98%) and 86.4% (95% CI, 67.6-95.6%), respectively (p=0.002). In lymph nodes with short axis ≥2 cm the diagnostic accuracy was 95.7% in EBUS-TBNA group and 93% in c-TBNA group (p=0.939); the sample adequacy was 68.7% and 68.3%, respectively (p=0.889); the sensitivity was 95.1% (95% CI, 83-99%) and 92.1%, respectively (95% CI, 78.7-97.7%) (p=0.898). The EBUS-TBNA in patients with lymph nodes size <2 cm presented a statistically significant difference in the DA, adequacy and sensitivity compared to c-TBNA procedure, while there were no significant differences in the DA, adequacy and sensitivity between EBUS-TBNA and c-TBNA in patients with lymph node size ≥2 cm. The results of our study indicated that the EBUS-TBNA should be the first-choice procedure for the diagnosis/staging in lung cancer patients with lymph node size <2 cm. In patients with lymph node size ≥2 cm, instead, both procedures can be used for the diagnosis/staging of lung cancer.

Lymph Node Size Alone is Not an Accurate Predictor of Metastases in Rectal Cancer: A Node-for-Node Comparative Study of Specimens and Histology

2015 ◽  
Vol 81 (12) ◽  
pp. 1263-1271 ◽  
Author(s):  
Yoshihiko Kono ◽  
Kazutomo Togashi ◽  
Kenichi Utano ◽  
Hisanaga Horie ◽  
Yasuyuki Miyakura ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Curative Intent ◽  
Accurate Predictor ◽  
Metastatic Rate ◽  
Glass Slides ◽  
Lymph Node Size ◽  
N Stage ◽  
Node Size

Although size criteria have been proposed to identify lymph node metastases in patients with rectal cancer, size may not be an accurate predictor. Specimens from consecutive rectal cancer patients who underwent curative-intent radical surgery were examined. The long and short axes of lymph nodes were measured on the glass slides using micrometer calipers. The pathologic diagnosis was used as the reference. The diagnostic accuracy of metastatic status according to lymph node size was evaluated. Overall, 1283 lymph nodes from 78 patients were reviewed. The metastatic rate correlates with the length of both the long and short axes. However, metastases were present even in 1-mm lymph nodes, and the metastatic rate exceeds 5 per cent in lymph nodes measuring 3 mm along both axes. Cutoff values of ≥4 mm and ≥3 mm for the long and short axes result in a sensitivity of 76 per cent and 79 per cent, and a specificity of 36 per cent and 33 per cent, respectively, for each axis. Size criteria alone do not accurately predict the N-stage of rectal cancer. Diminutive lymph nodes, which are not seen on imaging studies, can contain metastatic disease.

Effect of cholangitis on pre-operative evaluation of regional lymphadenopathy by CT in pancreato-biliary malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15651-e15651
Author(s):  
Abhijit Chandra ◽  
Vivek Gupta ◽  
Saket Kumar ◽  
Pradeep Joshi ◽  
Vishal Gupta ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Periampullary Cancer ◽  
Regional Lymph Nodes ◽  
Poor Prognostic Factor ◽  
Lymph Node Size ◽  
Ct Evaluation ◽  
History Of ◽  
Biliary Malignancies ◽  
Node Size

e15651 Background: Regional lymph nodes metastasis is a poor prognostic factor in pancreato-biliary malignancies. CT findings like lymph node size > 10mm, irregular shape, heterogenous enhancement, conglomeration and infiltration can suggest metastatic involvement. Cholangitis can induce reactive changes in regional lymph nodes. This study aimed to find if episodes of cholangitis interfere with the pre-operative CT evaluation of regional lymphadenopathy in pancreato-biliary malignancies. Methods: Regional lymph nodes metastasis is a poor prognostic factor in pancreato-biliary malignancies. CT findings like lymph node size > 10mm, irregular shape, heterogenous enhancement, conglomeration and infiltration can suggest metastatic involvement. Cholangitis can induce reactive changes in regional lymph nodes. This study aimed to find if episodes of cholangitis interfere with the pre-operative CT evaluation of regional lymphadenopathy in pancreato-biliary malignancies. Results: A total of 41 patients of gallbladder cancer and 20 patients of periampullary cancer were included. A total of 206 lymph node stations were sampled. In gallbladder cancer group, CT finding of lymph node size > 10mm, ill-defined borders and conglomeration; while intra-operative findings were node size > 10mm, hard consistency and necrosis on cut-section significantly predicted metastatic lymphadenopathy on univariate analysis. In multivariate analysis, size > 10mm measured intra-operatively was the only significant predictor of metastatic lymphadenopathy.21.9% patients (9/41) had history of cholangitis pre-operatively. In this subgroup, none of the CT characteristic or intra-operative nodal feature significantly predicted malignant involvement. In periampullary cancer, nodal necrosis on intra-operative cut-section was a significant predictor of malignant involvement in univariate, but not in multivariate analysis. Subgroup analysis of patients with history of cholangitis (10/20) did not reveal any significant pre-operative or intra-operative lymph nodal feature predicting malignant involvement. Conclusions: In patients with gallbladder or periampullary cancer with history of cholangitis, the typical CT characteristics or the intra-operative characteristics of regional lymph nodes cannot be relied on to predict metastatic lymph node involvement. Thus, cholangitis affects the clinical staging of these malignancies.

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