1. A process for maintaining 3 dimensional orientation between a tissue specimen excised from an area of investigation, and images of the surface of said area of investigation, to register histopathologic diagnoses of multiple locations within said specimen with corresponding locations on the surface of said area of investigation, comprising:
acquiring a reference image of said surface of said area of investigation;
marking at least two fiduciary lines on tissue of said area of investigation at appropriate positions as not to obscure or destroy diagnostically significant information;
acquiring a fiduciary image of the surface of said tissue with said fiduciary lines;
excising said tissue to form said tissue specimen;
inserting at least two parallel needles through said specimen;
acquiring a specimen image of said specimen and said inserted needles over an alignment grid;
fixing said specimen, whereby a fixed specimen is formed;
acquiring a fixed image of said fixed specimen and said inserted needles over said alignment grid;
forming a paraffin mold containing said fixed specimen and said inserted needles;
injecting different colored inks through said needles while withdrawing said needles from said fixed specimen, whereby different colored needle tracks are formed in said specimen;
sectioning said specimen to create specimen blocks having said different colored needle tracks;
further sectioning said specimen to cut said specimen blocks into specimen slices having different colored ink dots corresponding to said different colored needle tracks, whereby said different colored ink dots serve as reference points;
forming pathology images from said specimen slices;
performing histopathology analyses on said pathology images;
annotating said pathology images with histopathology annotations;
aligning said annotations with said fixed image using said reference points;
determining shrinkage between said fixed image and said annotations by comparing the distance between said needles on said grid in said fixed image with the distance between said reference points on said specimen slices in said pathology images;
registering said fixed image to said specimen image to account for shrinkage caused by fixation, by using locations of said needles in both of said images as landmarks; and
registering said specimen image to said fiduciary image to account for tissue translation and soft tissue movement using said fiduciary lines and geographical features of said area of investigation as landmarks;
registering said fiduciary image to said reference image to account for tissue translation and soft tissue movement using said geographical features;
whereby annotations of histopathologic diagnoses are provided for multiple locations on or under the surface of said specimen that are shown in said fiduciary image of said specimen.
2. A process according to claim 1, wherein said inserting step is performed using at least three parallel needles, whereby any bending of said specimen can be detected.
3. A process according to claim 1, wherein said fixing step is performed by immersing said specimen and said inserted needles in a fixing material selected from the group consisting of formaldehyde, tannic acid, glutaraldehyde, tannic acid, picric acid, absolute alcohol, potassium dichromate, mercuric chloride and osmium tetroxide.
4. A process according to claim 1, wherein said fixing step is performed using a process selected from the group consisting of rapid heating and quick-freezing of said specimen and said inserted needles.
5. A process for registering histopathologic diagnoses of multiple locations within a tissue specimen from an area of investigation with corresponding locations on the surface of said area of investigation, comprising:
maintaining three dimensional orientation between said specimen and said surface of said area under investigation by:
marking fiduciary lines on tissue of said area of investigation;
acquiring a fiduciary image of said area of investigation and said fiduciary lines;
excising said tissue to form said tissue specimen;
inserting at least two parallel needles through said specimen;
acquiring a specimen image of said specimen and said inserted needles over an alignment grid;
forming at least one colored needle track in said specimen using at least one of said needles;
sectioning said specimen into specimen slices having at least one colored ink dot corresponding to said at least one colored needle track, whereby said at least one colored ink dot and an uncolored dot formed by any uncolored needle track serve as reference points;
performing histopathology analyses on said specimen slices;
annotating pathology images of said specimen slices with histopathology annotations;
registering said annotations with said specimen image using said reference points;
determining shrinkage between said specimen image and said annotations by comparing the distance between said needles on said grid in said specimen image with the distance between said reference points; and
registering said specimen image to said fiduciary image using said fiduciary lines and geographical features of said area of investigation as landmarks;
whereby annotations of histopathologic diagnoses are provided for multiple locations on or under the surface of said area of investigation that are shown in said fiduciary image.
6. A process for maintaining three dimensional orientation between a tissue specimen from an area of investigation with corresponding locations on the surface of said area of investigation, comprising:
marking fiduciary lines on tissue of said area of investigation;
acquiring a fiduciary image of said area of investigation and said fiduciary lines;
excising said tissue to form said tissue specimen;
forming at least two parallel needle tracks in said specimen by inserting at least two parallel needles through said specimen;
coloring at least one of said needle tracks to form at least one colored needle track;
acquiring a specimen image of said specimen and said inserted needles over an alignment grid; and
sectioning said specimen into specimen slices having at least one colored ink dot corresponding to said at least one colored needle track, whereby said at least one colored ink dot and an uncolored dot formed by any uncolored needle track serve as reference points;
whereby images of said specimen slices can be registered to said specimen image using said reference points; and
whereby said specimen image can be registered to said fiduciary image using said fiduciary lines and geographical features of said area of investigation as landmarks.
7. A process for maintaining three dimensional orientation between a material specimen from an area of investigation with corresponding locations on the surface of said area of investigation, comprising:
marking fiduciary lines on material of said area of investigation;
acquiring a fiduciary image of said area of investigation and said fiduciary lines;
excising said material to form said material specimen;
forming at least two tracks through said specimen;
coloring at least one of said tracks to form at least one colored track;
acquiring a specimen image of said specimen and said tracks over an alignment grid; and
sectioning said specimen into specimen slices having at least one colored ink dot corresponding to said at least one colored track, whereby said at least one colored ink dot and an uncolored dot formed by any uncolored track serve as reference points;
whereby images of said specimen slices can be registered to said specimen image using said reference points; and
whereby said specimen image can be registered to said fiduciary image using said fiduciary lines and geographical features of said area of investigation as landmarks.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
We claim:
1. Electroprocessed fibrin.
2. The electroprocessed fibrin of claim 1, in a matrix.
3. The electroprocessed fibrin matrix of claim 2, further comprising cells.
4. The electroprocessed fibrin matrix of claim 2, further comprising one or more substances.
5. The electroprocessed fibrin matrix of claim 4, wherein the one or more substances is a growth factor, differentiation inducer, anti-oxidant, vitamin, hormone, nucleic acid, drug, peptide, nucleic acid, emollient, humectant, conditioner or cosmetic
6. An engineered tissue comprising the electroprocessed fibrin matrix of claim 2 and cells.
7. The engineered tissue of claim 6, further comprising one or more substances.
8. The engineered tissue of claim 6, wherein the cells are stem cells or differentiated cells.
9. A method of delivering a substance to a desired location comprising;
adding a substance to the electroprocessed fibrin of claim 1; and,
placing the electroprocessed fibrin containing the substance in the desired location.
10. A method of delivering a substance to a desired location comprising;
adding a substance to the electroprocessed fibrin matrix of claim 2; and,
placing the electroprocessed fibrin matrix containing the substance in the desired location.
11. A method of treating a wound, comprising applying the electroprocessed fibrin of claim 1 to the wound.
12. A method of treating a wound, comprising applying the electroprocessed fibrin matrix of claim 2 to the wound.
13. A method of providing hemostasis, comprising applying the electroprocessed fibrin of claim 1 to a site of bleeding.
14. A method of providing hemostasis, comprising applying the electroprocessed fibrin matrix of claim 2 to a site of bleeding.
15. A method of evaluating a biological response of a cell to a substance, comprising:
applying the substance to the electroprocessed fibrin matrix and cells of claim 3; and,
evaluating the biological response of the cell.
16. The method of claim 15, wherein the cell is a cancer cell.
17. A method of manufacturing the electroprocessed fibrin of claim 1, comprising:
electrodepositing one or more electrically-charged solutions comprising fibrin or molecules capable of forming fibrin onto a grounded target substrate under conditions effective to electrodeposit fibrin or molecules capable of forming fibrin on said substrate to form the electroprocessed fibrin.
18. A method of manufacturing the electroprocessed fibrin matrix of claim 2, comprising:
electrodepositing one or more electrically-charged solutions comprising fibrin or molecules capable of forming fibrin onto a grounded target substrate under conditions effective to electrodeposit fibrin or molecules capable of forming fibrin on said substrate to form the electroprocessed fibrin matrix.
19. A method of manufacturing the engineered tissue of claim 6, comprising:
electrodepositing one or more electrically-charged solutions comprising fibrin or molecules capable of forming fibrin, and cells, onto a grounded target substrate under conditions effective to deposit the electroprocessed fibrin or molecules capable of forming fibrin and the cells onto the substrate.
20. A method of manufacturing the engineered tissue of claim 6, comprising:
electrodepositing one or more electrically-charged solutions comprising fibrin or molecules capable of forming fibrin onto a grounded target substrate under conditions effective to deposit the electroprocessed fibrin or molecules capable of forming fibrin; and,
applying cells onto the substrate or into a stream of the electroprocessed fibrin or molecules capable of forming fibrin, wherein the stream is located between the grounded target substrate and the solutions.
21. An electroprocessed fibrin matrix.
22. An engineered tissue comprising an electroprocessed fibrin matrix and cells.