Friday, 12 December 2014

Imaging lesions earlier

Pulli B, Bure L, Wojtkiewicz GR, Iwamoto Y, Ali M, Li D, Schob S, Li-Chun Hsieh K, Jacobs AH, Chen JW. Multiple Sclerosis: Myeloperoxidase Immunoradiology Improves Detection of Acute and Chronic Disease in Experimental Model. Radiology. 2014 Dec 10:141495. [Epub ahead of print]

Purpose To test if MPO myeloperoxidase -Gd, a gadolinium-based magnetic resonance (MR) imaging probe that is sensitive and specific for the proinflammatory and oxidative enzyme myeloperoxidase ( MPO myeloperoxidase ), which is secreted by certain inflammatory cells, is more sensitive than diethylenetriaminepentaacetic acid ( DTPA diethylenetriaminepentaacetic acid )-Gd in revealing early subclinical and chronic disease activity in the brain in experimental autoimmune encephalomyelitis ( EAE experimental autoimmune encephalomyelitis ), a mouse model of multiple sclerosis. 
Materials and Methods The protocol for animal experiments was approved by the institutional animal care committee. A total of 61 female SJL mice were induced with EAE experimental autoimmune encephalomyelitis . Mice underwent MPO myeloperoxidase -Gd- or DTPA diethylenetriaminepentaacetic acid -Gd-enhanced MR imaging on days 6, 8, and 10 after induction, before clinical disease develops, and during chronic disease at remission and the first relapse. Brains were harvested at these time points for flow cytometric evaluation of immune cell subtypes and immunohistochemistry. Statistical analysis was performed, and P < .05 was considered to indicate a significant difference. 
Results MPO myeloperoxidase -Gd helps detect earlier (5.2 vs 2.3 days before symptom onset, P = .004) and more (3.1 vs 0.3, P = .008) subclinical inflammatory lesions compared with DTPA diethylenetriaminepentaacetic acid -Gd, including in cases in which there was no evidence of overt blood-brain barrier ( BBB blood-brain barrier ) breakdown detected with DTPA diethylenetriaminepentaacetic acid -Gd enhancement. The number of MPO myeloperoxidase -Gd-enhancing lesions correlated with early infiltration of MPO myeloperoxidase -secreting monocytes and neutrophils into the brain (r = 0.91). MPO myeloperoxidase -Gd also helped detect more lesions during subclinical disease at remission (5.5 vs 1.3, P = .006) and at the first relapse (9.0 vs 2.7, P = .03) than DTPA diethylenetriaminepentaacetic acid -Gd, which also correlated well with the presence and accumulation of MPO myeloperoxidase -secreting inflammatory cells in the brain (r = 0.93). 
Conclusion MPO myeloperoxidase -Gd specifically reveals lesions with inflammatory monocytes and neutrophils, which actively secrete MPO myeloperoxidase . These results demonstrate the feasibility of detection of subclinical inflammatory disease activity in vivo, which is different from overt BBB blood-brain barrier breakdown.

People equate Gadolinium enhancement with white blood cell infiltration into the CNS, but it is perhaps a marker of fluid movement during blood brain barrier dysfunction and in animals gadolinium leakage is more extensive than the lesions that you see histologically. In this study they found that gadolinium enhancement occurred about 2 days before signs of disease. This is consistent with what we found in the past when rodents show a bit of pre-clinical weight loss about 2 days before onset of signs. This is when the secondary wave of infiltrating cells are accumulating. When we used radioactive gadolinium as a tracer we could find leakage even earlier indicating that things were occurring earlier than this. The scanner is less sensitive than using a radioactive tracer, but using a different type of imaging agent they can find evidence of events occurring much earlier in the CNS tissue. Maybe they are detecting the first wave of infiltrating cells, as it is clear that damage can occur before overt clinical signs. Some people think that white blood cells park in the lung before they go to the central nervous system after they leave the lymph glands. Is there enough time for this to happen if the lesions are developing much earlier than people think? 

What is the logic of parking or licencing cells in the lung before they go into the brain, it seems an overly complicated system? 

No comments:

Post a Comment

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.