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Induction of Hyperintense Signal on T2-Weighted MR Images Correlates with Infusion Distribution from Intracerebral Convection-Enhanced Delivery of a Tumor-Targeted Cytotoxin

¹ Department of Surgery, Duke University Medical Center, Durham, NC 27710.
² Therataxis, Inc., Baltimore, MD 21218.
³ Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710.
⁴ NeoPharm, Inc., Waukegan, IL 60085.
⁵ BrainLAB AG, Feldkirchen, Germany.
⁶ Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
⁷ Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852.

View larger version (77K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Preinfusion axial T2-weighted image shows catheter trajectory (green line) and catheter tip in occipital lobe.

View larger version (64K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 24 hours after beginning of infusion shows development of new hyperintense signal abnormality at catheter tip.

View larger version (77K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 48 hours after beginning of infusion shows increase in hyperintense signal at catheter tip.

View larger version (68K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 96 hours after beginning of infusion shows prominent region of hyperintense signal at catheter tip.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Superimposition on D of intraparenchymal distribution from 48-hour 123I-human serum albumin SPECT at 50% isodose level (orange).

View larger version (61K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1F —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Preinfusion axial T2-weighted image shows catheter trajectory (green line) and catheter tip in occipital lobe.

View larger version (72K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1G —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 24 hours after beginning of infusion shows development of new hyperintense signal abnormality at catheter tip.

View larger version (49K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1H —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 48 hours after beginning of infusion shows increase in hyperintense signal at catheter tip.

View larger version (64K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1I —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Axial T2-weighted image 96 hours after beginning of infusion shows prominent region of hyperintense signal at catheter tip.

View larger version (64K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1J —19-year-old man (A-E) and 56-year-old man (F-J) with glioblastoma multiforme. Serial increases in MR signal intensity after successful convection-enhanced infusion in two patients with little or no preexisting signal abnormality directly at catheter tip. In both patients morphology of region of hyperintense signal abnormality on MRI closely matches distribution of infusate seen on SPECT. Human figure indicates imaging plane. Blue line indicates plane perpendicular to tip of catheter. Green line indicates catheter trajectory. Superimposition on I of intraparenchymal distribution from 48-hour 123I-human serum albumin SPECT at 50% isodose level (green).

View larger version (81K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Oblique sagittal T2-weighted image shows trajectory of catheter (red line) and superimposed coregistered SPECT signal (yellow outline) around tip of catheter at 50% isodose level. Catheter tip is inappropriately adjacent to sulcus.

View larger version (91K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Oblique coronal T2-weighted image oriented 90° to A shows catheter trajectory (red line), superimposed coregistered SPECT signal at 50% isodose level, and portions of resection cavity medial to catheter trajectory. A sulcus, through which infusate has leaked into subarachnoid CSF spaces, is seen extending approximately 1 cm along distal end of catheter tip. Long axis of region of SPECT signal extends toward subarachnoid space (rather than circumferentially surrounding catheter tip) indicating leakage of infusate into subarachnoid space (yellow outline). Leakage accounts for absence of development of hyperintense signal adjacent to catheter tip.

View larger version (74K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Oblique axial T2-weighted image oriented 90° to A and B shows tip of catheter (red dot) en face in sulcus. Because of catheter placement in sulcus, trajectory of infusate (yellow outline) is not intraparenchymal but extends across multiple sulci in subarachnoid space.

View larger version (69K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Axial T2-weighted image depicting trajectory of second catheter (turquoise line) shows end of catheter projecting into subarachnoid space and wholly extraparenchymal infusate volume (outline). Hyperintense signal is not present around catheter tip.

View larger version (49K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Reconstructed image in coronal plane shows catheter (turquoise line) piercing pial surface and infusate accumulation (outline) within basilar cisterns.

View larger version (38K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2F —19-year-old man with glioblastoma multiforme. Two types of infusion failure were seen in this patient. Forty-eight hours after initiation of convection-enhanced infusion, leakage of infusate into subarachnoid CSF space occurred, and hyperintense signal did not develop on T2-weighted MR images. A-C, Images show failure due to catheter crossing sulcus within backflow region. D-F, Images show failure due to placement of catheter tip within subarachnoid space. Human figure indicates imaging plane. Blue line and indicates plane perpendicular to catheter shown in C and F. Thick red and thicker and lighter blue indicate catheter trajectories. Reconstructed image in sagittal plane shows catheter tip (dot) within center of extraparenchymal infusate volume (outline).

View larger version (8K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3 —Line plot shows volume of distribution of 123I-human serum albumin measured at 50% isodose level with SPECT on x-axis and volume of region of hyperintense signal on T2-weighted MR images 24 and 48 hours after start of infusion on y-axis for catheters placed into regions without substantial hyperintensity before infusion. Plot shows correlation between these two measures (r2 = 0.9502 for all data points, r2 = 0.9094 for 24-hour data points, and r2 = 0.9412 for 48-hour data points).

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