Visualization of a biopsy trajectory.

<p>The trajectory is defined by the coordinates of the entry point E(104/128/114) and target point T(112/141/53) and biopsy specimens are taken along the trajectory, mainly close to the target point.</p

Scatterplot of ADC and cellularity with regression line and 95% confidence interval.

<p>Aggregated mean ADC and cellularity values per patient are displayed (37 patients). Pearson’s r = -0.40, p = 0.007; Spearman’s ρ = -0.48, p = 0.002</p

Comparison of two exemplary patients (patient 1: A-D, patient 2: E-H).

<p>A,E: Intraoperative cT1-scans. The biopsy location on this slice is marked by a white crosshair. B,F: Preoperative ADC-maps, which have been registered to intraoperative scans as described. The biopsy location on this slice is marked by a white crosshair. C,G: Scanned biopsy specimens of the respective location (HE stain, x20 magnification). D,H: semi-automatic cell counting on 8-bit images by the ImageJ plugin ITCN. Detected cells are marked with red dots. For patient 1(A-D), analysis yielded ADC = 658mm²/s and cellularity = 16840 cells/mm². For patient 2 (E-H), it was ADC = 1479mm²/s and cellularity = 2208 cells/mm².</p

Cell densities within MRI classifications.

<p>Cell densities within MRI classifications.</p

Correlation of cT1 MRI and histology.

<p>A) Target point T with its coordinates in an axial slide of the intraoperative cT1 MRI of the patient from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169292#pone.0169292.g001" target="_blank">Fig 1a</a>. It lies in the CE area. B) Corresponding slice of the 1mm³ biopsy specimen (HE stain) in x20 magnification which was classified as “necrosis with cellular component”. This type of histology occurred in 31% of all biopsies originating from CE. C) Calculated biopsy point C with its coordinates in an axial slide of the intraoperative cT1 MRI of an 82-year-old patient with glioblastoma. It lies in the CE area. D) Corresponding slice of the 1mm³ biopsy specimen (HE stain) in x20 magnification which was classified as “viable tumor tissue”. This type of histology occurred in 60% of all biopsies originating from CE. E) Different biopsy point D with its coordinates along the trajectory in the same patient. It lies in the NEC area. F) Corresponding slice of the 1mm³ biopsy specimen (HE stain) in x20 magnification which was classified as “pure necrosis”. This type of histology occurred in 4% of all biopsies originating from NEC.</p

Boxplots of the cell densities in each MRI compartment.

<p>A) Cell densities for all biopsies (“viable tumor cells”, “necrosis with cellular component”, “pure necrosis”, “blood cells”). B) Cell densities in biopsies with “viable tumor cells” only. NE = non-enhancing part on cT1; CE = contrast enhancement on cT1; NEC = Necrosis on cT1.</p

Histological composition of the different MRI classifications.

<p>For all 561 biopsy samples, the relative frequency of the different histologic classifications within each MRI classification is displayed. NE = non-enhancing part on cT1; CE = contrast enhancement on cT1; NEC = Necrosis on cT1.</p

Patient-individual Spearman correlation coefficients (r_Sp) with 95% confidence intervals.

<p>Positive correlations are marked blue, negative correlations are red, insignificant correlations (p>0.05) are grey. No trend towards any correlation between MTR_asym and ADC could be found in the CE-T1 tumor region (left diagram), since correlation coefficients scatter around r_Sp≈0. For the T2 edema region (right diagram) a trend towards a positive correlation could be observed. Eight of fifteen patients correlate weakly or moderately positive, while seven coefficients are insignificant (n = 4) or too low to claim an association (n = 3). The trend towards a positive correlation within the T2 edema region is suspected to be due its more homogeneous structure, compared to the CE-T1 tumor which is characterized by different cell types, vasculogenesis and necrotic foci.</p

Correlation analysis of MTR_asym values and ADC values with the cell density of corresponding biopsy sites.

<p>* significant correlations are marked. r_Sp = Spearman rho</p><p>Correlation analysis of MTR_asym values and ADC values with the cell density of corresponding biopsy sites.</p

Correlation of biopsy point S with histology and semi-automatic cell counting.

<p>A) Biopsy point S is located in the NE area on an axial slide of the intraoperative cT1 MRI. B) Corresponding slice of the 1mm³ biopsy specimen (HE stain) in x20 magnification which was classified as “viable tumor tissue”. This type of histology occurred in 89% of all biopsies originating from NE. C) Example of semi-automatic cell counting with the ImageJ plugin ITCN. Correctly recognized tumor cells are marked red. Yellow dots are falsely detected areas of apoptotic cells or intercellular space.</p