scholarly journals Validation of in vivo nodal staging of solid malignancies with USPIO-enhanced MRI: a workflow protocol

2020 ◽  
Author(s):  
Daphne A.J.J. Driessen ◽  
Didi J.J.M. de Gouw ◽  
Rutger C.H. Stijns ◽  
Geke Litjens ◽  
Bas Israël ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Ex Vivo ◽  
Mr Images ◽  
Trial Register ◽  
Enhanced Mri ◽  
Cancer Types ◽  
Node Metastases

Abstract BackgroundIn various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. MethodsIn patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious for harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla (T) preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR-images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. ResultsMatching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology which allowed for analyses on nodal, or at least on nodal station level.ConclusionsA workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed analysis at nodal level, or at least nodal station level of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced MRI detected lymph nodes. Trial registrationVALINODE data is collected from patients undergoing USPIO-enhanced MRI in the clinical setting. Therefore, the trial has not been registered in an online trial register. 7TNANO1 is registered at Clinicaltrials.gov: NCT02751606, April 26 2016 (https://clinicaltrials.gov/ct2/show/NCT02751606). NANO-PANC is registered at Clinicaltrials.gov: NCT04311047, March 17 2020 (https://www.clinicaltrials.gov/ct2/show/NCT04311047). PRECIES is registered in the Dutch Trial Register: NTR6072, August 5 2016 (https://www.trialregister.nl/trial/5797). USPIO-NECK is registered at Clinicaltrials.gov: NCT03817307, January 25 2019 (https://clinicaltrials.gov/ct2/show/NCT03817307).

P65 USPIO-MRI FOR PRE-OPERATIVE LYMPH NODE STAGING AFTER NEOADJUVANT CHEMORADIOTHERAPY: FEASIBILITY AND VALIDATION FRAMEWORK

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
D J. J. M. de Gouw ◽  
B R. Klarenbeek ◽  
M C Maas ◽  
C Slagt ◽  
J Mühling ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Esophageal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Ex Vivo ◽  
Enhanced Mri ◽  
Mean Diameter ◽  
Controlled Mechanical Ventilation ◽  
Node Metastases

Abstract Background Extensive lymph node dissections during esophagectomy may be omitted in patients with esophageal cancer without lymph node metastases, reducing associated morbidity. A promising technique to detect lymph node metastases is MRI with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, ferumoxtran-10). To validate USPIO-enhanced MRI in patients with esophageal cancer, a framework is designed to compare lymph nodes of the MRI scans with histopathology data on a node-to-node level. Methods USPIO-nanoparticles are intravenously infused 24 to 36 hours before MRI. USPIO-enhanced MRI is performed before and after nCRT. After nCRT, patients are scanned under general anesthesia immediately prior to surgery in the MR system of the hybrid MITeC operation room with controlled mechanical ventilation. During controlled prolonged apneu, a four-minute iron-sensitive MRI acquisition is used to visualize suspicious esophageal lymph nodes without motion artefacts. Resected specimens, still containing USPIO, are measured ex-vivo in a preclinical 7T MR system before histopathological examination. A radiological assessment of the presence of suspicious lymph nodes in-vivo is matched to the ex-vivo nodes on preclinical MRI, providing the ground truth for the presence of metastases. Results Currently, five patients have completed the full study protocol. Two patients underwent the first UPSIO-MRI but did not undergo surgery due to progressive disease. First results show that MRI under anesthesia prior to surgery with controlled mechanical ventilation was possible resulting in a clinically relevant spatial resolution to visualize possibly malignant lymph nodes. In these five patients, the radiologist found 58 lymph nodes with a mean diameter of 8.4 mm before nCRT and 40 lymph nodes with a mean diameter of 7.4 mm after nCRT. In total, 126 lymph nodes were analyzed by histopathology. Suspicious nodes were identified and could be matched using corresponding anatomical landmarks to the ex-vivo MRI, which showed good visual agreement with esophageal specimen after resection. Conclusions We performed USPIO-enhanced MRI in patients with esophageal cancer and proposed a method to validate USPIO-enhanced MRI to detect suspicious lymph nodes in these patients. Results on the feasibility of USPIO-enhanced MRI to detect metastatic lymph nodes after nCRT are still awaited.

Assessment of cervical lymph node metastases using indirect computed tomography lymphography with iopamidol in a tongue VX2 carcinoma model

2011 ◽  
Vol 125 (8) ◽  
pp. 820-828 ◽  
Author(s):  
Y Shu ◽  
X Xu ◽  
Z Wang ◽  
W Dai ◽  
Y Zhang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Cervical Lymph Node ◽  
Cervical Lymph Nodes ◽  
Cervical Lymph Node Metastases ◽  
Computed Tomography Images ◽  
Vx2 Carcinoma ◽  
Node Metastases

AbstractObjective:To investigate the performance of indirect computed tomography lymphography with iopamidol for detecting cervical lymph node metastases in a tongue VX2 carcinoma model.Materials and methods:A metastatic cervical lymph node model was created by implanting VX2 carcinoma suspension into the tongue submucosa of 21 rabbits. Computed tomography images were obtained 1, 3, 5, 10, 15 and 20 minutes after iopamidol injection, on days 11, 14, 21 (six rabbits each) and 28 (three rabbits) after carcinoma transplantation. Computed tomography lymphography was performed, and lymph node filling defects and enhancement characteristics evaluated.Results:Indirect computed tomography lymphography revealed bilateral enhancement of cervical lymph nodes in all animals, except for one animal imaged on day 28. There was significantly slower evacuation of contrast in metastatic than non-metastatic nodes. A total of 41 enhanced lymph nodes displayed an oval or round shape, or local filling defects. One lymph node with an oval shape was metastatic (one of 11, 9.1 per cent), while 21 nodes with filling defects were metastatic (21/30, 70 per cent). The sensitivity, specificity, accuracy, and positive and negative predictive values when using a filling defect diameter of 1.5 mm as a diagnostic criterion were 86.4, 78.9, 82.9, 82.6 and 83.3 per cent, respectively.Conclusion:When using indirect computed tomography lymphography to detect metastatic lymph nodes, filling defects and slow evacuation of contrast agent are important diagnostic features.

scholarly journals COL16A1 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Lymphoid Organ ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals COL6A1 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Lymphoid Organ ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals TSHZ3 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals TMEM98 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals CD69 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals DIAPH2 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that diaphanous homolog 2, encoded by DIAPH2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. DIAPH2 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of DIAPH2 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of DIAPH2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.

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