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EJNMMI Res
2015 Dec 01;51:64. doi: 10.1186/s13550-015-0138-7.
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A method for accurate spatial registration of PET images and histopathology slices.
Puri T
,
Chalkidou A
,
Henley-Smith R
,
Roy A
,
Barber PR
,
Guerrero-Urbano T
,
Oakley R
,
Simo R
,
Jeannon JP
,
McGurk M
,
Odell EW
,
O'Doherty MJ
,
Marsden PK
.
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BACKGROUND: Accurate alignment between histopathology slices and positron emission tomography (PET) images is important for radiopharmaceutical validation studies. Limited data is available on the registration accuracy that can be achieved between PET and histopathology slices acquired under routine pathology conditions where slices may be non-parallel, non-contiguously cut and of standard block size. The purpose of this study was to demonstrate a method for aligning PET images and histopathology slices acquired from patients with laryngeal cancer and to assess the registration accuracy obtained under these conditions.
METHODS: Six subjects with laryngeal cancer underwent a (64)Cu-copper-II-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) PET computed tomography (CT) scan prior to total laryngectomy. Sea urchin spines were inserted into the pathology specimen to act as fiducial markers. The specimen was fixed in formalin, as per standard histopathology operating procedures, and was then CT scanned and cut into millimetre-thick tissue slices. A subset of the tissue slices that included both tumour and fiducial markers was taken and embedded in paraffin blocks. Subsequently, microtome sectioning and haematoxylin and eosin staining were performed to produce 5-μm-thick tissue sections for microscopic digitisation. A series of rigid registration procedures was performed between the different imaging modalities (PET; in vivo CT-i.e. the CT component of the PET-CT; ex vivo CT; histology slices) with the ex vivo CT serving as the reference image. In vivo and ex vivo CTs were registered using landmark-based registration. Histopathology and ex vivo CT images were aligned using the sea urchin spines with additional anatomical landmarks where available. Registration errors were estimated using a leave-one-out strategy for in vivo to ex vivo CT and were estimated from the RMS landmark accuracy for histopathology to ex vivo CT.
RESULTS: The mean ± SD accuracy for registration of the in vivo to ex vivo CT images was 2.66 ± 0.66 mm, and the accuracy for registration of histopathology to ex vivo CT was 0.86 ± 0.41 mm. Estimating the PET to in vivo CT registration accuracy to equal the PET-CT alignment accuracy of 1 mm resulted in an overall average registration error between PET and histopathology slices of 3.0 ± 0.7 mm.
CONCLUSIONS: We have developed a registration method to align PET images and histopathology slices with an accuracy comparable to the spatial resolution of the PET images.
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Fig. 3. Laryngeal pathology specimen. Example of a laryngeal pathology specimen from a patient with advanced laryngeal cancer that was included in the study. The exact anatomical orientation (left to right and top to bottom) and the consecutive cutting of the samples are displayed, as recorded at the time of the slicing by the pathology lab staff
Fig. 4. Slicing of excised specimen. A schematic diagram showing (left) the excised specimen, (centre) a ~5-mm-thick tissue slice and (right) a 5-μm-thick tissue slice that has been stained. A relevant section is taken from the 5-mm slice which is then embedded in paraffin prior to microtome cutting to obtain the 5-μm-thick tissue slices
Fig. 5. In vivo CT (left) and the corresponding ex vivo CT (right) of the pathology specimen. The ex vivo CT corresponds to the area outlined by the red box. Large deformations occurring due to the surgical excision can be seen
Fig. 6. Identification of corresponding CT planes and histology slices. Example showing how corresponding histology slices and (ex vivo) CT planes are identified. The RMS distance is calculated using either four spine fiducial markers (blue line) or four spine fiducial markers and one anatomical landmark (red line). Although there is approximate agreement between the two methods, the use of landmarks leads to more precise identification as the landmarks are often confined to one or two consecutive axial slices. Although the measurements using the fiducial markers only (blue line) leads to smaller RMSE, both methods lead to a very similar position of the global minimum. The CT slice that showed corresponding to the minimum RMSE was chosen as that corresponding with the given histopathology slice. RMSE root mean square error
Fig. 7. Fused PET and CT components of PET-CT scan. Coronal view of fused co-registered PET and ex vivo CT data for patient number 4. Very good alignment between the two data sets can be observed by using the tracheostomy as a reference point
Fig. 8. Registered PET, ex vivo CT and histology images. (a–c) show registered images of PET, ex vivo CT and histology from two different subjects. Regions in PET and ex vivo CT that correspond to histology are marked with a red outline. Yellow markers in (c) show the sea urchin spine markers that were clearly visible on the ex vivo CT and histology images
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