Image-guided convection-enhanced delivery of gemcitabine to the brainstem

2007 ◽  
Vol 106 (2) ◽  
pp. 351-356 ◽  
Author(s):  
Gregory J. A. Murad ◽  
Stuart Walbridge ◽  
Paul F. Morrison ◽  
Nicholas Szerlip ◽  
John A. Butman ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Histological Analysis ◽  
Chemotherapeutic Agent ◽  
Volume Of Distribution ◽  
Magnetic Resonance Images ◽  
Quantitative Autoradiography ◽  
Therapeutic Application ◽  
Convection Enhanced Delivery ◽  
Therapeutic Doses

Object To determine if the potent antiglioma chemotherapeutic agent gemcitabine could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution using a surrogate magnetic resonance (MR) imaging tracer, the authors used convection-enhanced delivery to perfuse the primate brainstem with gemcitabine and Gd–diethylenetriamine pentaacetic acid (DTPA). Methods Six primates underwent convective brainstem perfusion with gemcitabine (0.4 mg/ml; two animals), Gd-DTPA (5 mM; two animals), or a coinfusion of gemcitabine (0.4 mg/ml) and Gd-DTPA (5 mM; two animals), and were killed 28 days afterward. These primates were observed over time clinically (six animals), and with MR imaging (five animals), quantitative autoradiography (one animal), and histological analysis (all animals). In an additional primate, 3H-gemcitabine and Gd-DTPA were coinfused and the animal was killed immediately afterward. In the primates there was no histological evidence of infusate-related tissue toxicity. Magnetic resonance images obtained during infusate delivery demonstrated that the anatomical region infused with Gd-DTPA was clearly distinguishable from surrounding noninfused tissue. Quantitative autoradiography confirmed that Gd-DTPA tracked the distribution of 3H-gemcitabine and closely approximated its volume of distribution (mean volume of distribution difference 13.5%). Conclusions Gemcitabine can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and at volumes that are higher than those considered clinically relevant. Moreover, MR imaging can be used to track the distribution of gemcitabine by adding Gd-DTPA to the infusate. This delivery paradigm should allow for direct therapeutic application of gemcitabine to brainstem gliomas while monitoring its distribution to ensure effective tumor coverage and to maximize safety.

Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion

2002 ◽  
Vol 97 (4) ◽  
pp. 905-913 ◽  
Author(s):  
Russell R. Lonser ◽  
Stuart Walbridge ◽  
Kayhan Garmestani ◽  
John A. Butman ◽  
Hugh A. Walters ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Histological Analysis ◽  
Volume Of Distribution ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Large Molecular Weight ◽  
Fine Print

Object. Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood—brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem. Methods. Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 µl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 ± 1.2 (mean ± standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track. Conclusions. First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes.

Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles

2007 ◽  
Vol 107 (3) ◽  
pp. 560-567 ◽  
Author(s):  
Nicholas J. Szerlip ◽  
Stuart Walbridge ◽  
Linda Yang ◽  
Paul F. Morrison ◽  
Jeffrey W. Degen ◽  
...  
Keyword(s):  
White Matter ◽  
Mr Imaging ◽  
Real Time ◽  
Volume Of Distribution ◽  
Quantitative Autoradiography ◽  
Clinical Effects ◽  
Convection Enhanced Delivery ◽  
Histological Data ◽  
The Central Nervous System ◽  
The Mean

Object Despite recent evidence showing that convection-enhanced delivery (CED) of viruses and virus-sized particles to the central nervous system (CNS) is possible, little is known about the factors influencing distribution of these vectors with convection. To better define the delivery of viruses and virus-sized particles in the CNS, and to determine optimal parameters for infusion, the authors coinfused adeno-associated virus ([AAV], 24-nm diameter) and/or feru-moxtran-10 (24 nm) by using CED during real-time magnetic resonance (MR) imaging. Methods Sixteen rats underwent intrastriatal convective coinfusion with 4 μl of 35S-AAV capsids (0.5–1.0 × 1014 viral particles/ml) and increasing concentrations (0.1, 0.5, 1, and 5 mg/ml) of a similar sized iron oxide MR imaging agent (ferumoxtran-10). Five nonhuman primates underwent either convective coinfusion of 35S-AAV capsids and 1 mg/ml ferumoxtran-10 (striatum, one animal) or infusion of 1 mg/ml ferumoxtran-10 alone (striatum in two animals; frontal white matter in two). Clinical effects, MR imaging studies, quantitative autoradiography, and histological data were analyzed. Results Real-time, T2-weighted MR imaging of ferumoxtran-10 during infusion revealed a clearly defined hypo-intense region of perfusion. Quantitative autoradiography confirmed that MR imaging of ferumoxtran-10 at a concentration of 1 mg/ml accurately tracked viral capsid distribution in the rat and primate brain (the mean difference in volume of distribution [Vd] was 7 and 15% in rats and primates, respectively). The Vd increased linearly with increasing volume of infusion (Vi) (R2 = 0.98). The mean Vd/Vi ratio was 4.1 ± 0.2 (mean ± standard error of the mean) in gray and 2.3 ± 0.1 in white matter (p < 0.01). The distribution of infusate was homogeneous. Postinfusion MR imaging revealed leakback along the cannula track at infusion rates greater than 1.5 μl/minute in primate gray and white matter. No animal had clinical or histological evidence of toxicity. Conclusions The CED method can be used to deliver AAV capsids and similar sized particles to the CNS safely and effectively over clinically relevant volumes. Moreover, real-time MR imaging of ferumoxtran-10 during infusion reveals that AAV capsids and similar sized particles have different convective delivery properties than smaller proteins and other compounds.

scholarly journals Atypical, polyarticular lipoma arborescens in a child

2016 ◽  
Vol 144 (11-12) ◽  
pp. 650-653
Author(s):  
Robert Semnic ◽  
Radoje Simic ◽  
Slavisa Djuricic ◽  
Oto Adjic ◽  
Filip Vanhoenacker
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Open Surgery ◽  
Literature Search ◽  
Histological Analysis ◽  
Rare Tumor ◽  
Rare Entity ◽  
Lipoma Arborescens ◽  
Diagnostic Protocol ◽  
The Right

Introduction. Lipoma arborescens is a rare, tumor-like lesion commonly involving synovial joints and less commonly bursae and synovial tendon sheaths. Case Outline. We report a case of a 12-year-old boy with symmetric involvement of the bicipitoradial bursae, synovial sheaths of extensor compartments of both hands and medial ankles. The diagnosis of polyarticular lipoma arborescens was proposed on magnetic resonance (MR) imaging and this diagnosis was histologically proven after biopsy of the bursae and later by open surgery of the synovial sheath of the right ankle tendons. Literature search was performed and twelve cases with polyarticular involvement were analyzed. Lipoma arborescens commonly involves suprapatellar recess of the knee and very rarely other joints or bursae. Histological analysis revealed an accompanying non-necrotizing granulomatous synovial inflammation. Conclusion. Polyarticular lipoma arborescens is a rare entity and symmetrical involvement of the joints other than the knees is exceedingly rare. MR imaging plays a significant role in the diagnostic protocol, and the characteristic fatty signal on MR imaging is highly suggestive of lipoma arborescens.

High-field magnetic resonance imaging in patients with moyamoya disease

2001 ◽  
Vol 94 (2) ◽  
pp. 233-237 ◽  
Author(s):  
Atsuko Harada ◽  
Yukihiko Fujii ◽  
Yuichiro Yoneoka ◽  
Shigekazu Takeuchi ◽  
Ryuichi Tanaka ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Healthy Volunteers ◽  
Moyamoya Disease ◽  
Cerebral Circulation ◽  
High Field ◽  
Magnetic Resonance Images ◽  
Cerebral Hypoperfusion ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to assess the utility of high-field magnetic resonance (MR) imaging as a quantitative tool for estimating cerebral circulation in patients with moyamoya disease. Methods. Eighteen patients with moyamoya disease who were scheduled to undergo revascularization surgery and 100 healthy volunteers were examined using T2-reversed MR imaging performed using a 3-tesla system. Ten of the 18 patients underwent a second study between 1 year and 3 years after revascularization. Magnetic resonance images obtained in the patients with moyamoya disease were statistically analyzed and compared with those obtained in healthy volunteers. The MR imaging findings were also correlated with results of single-photon emission computerized tomography and conventional cerebral angiography studies. Transverse lines in the white matter (medullary streaks) were observed in almost all persons. In healthy volunteers, the diameter sizes of the medullary streaks increased significantly with age (p < 0.001). Multiple logistic regression analysis revealed that age-adjusted medullary streak diameters were significantly larger in patients with moyamoya disease (p < 0.001). Diameter sizes also increased significantly with the increased severity of cerebral hypoperfusion (p < 0.001) and a higher angiographically determined stage of the disease (p < 0.001). Diameter sizes decreased significantly after surgery (p < 0.001). Conclusions. The increases in medullary streak diameters observed in patients with moyamoya disease appear to represent vessels dilated due to cerebral hypoperfusion. High-field T2-reversed MR imaging is useful in estimating cerebral circulation in patients with moyamoya disease.

scholarly journals High-resolution 3T magnetic resonance imaging and histological analysis of capsuloligamentous complex of the first metatarsophalangeal joint

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jin-e Wang ◽  
Rong-jie Bai ◽  
Hui-li Zhan ◽  
Wen-ting Li ◽  
Zhan-hua Qian ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
High Resolution ◽  
Mr Imaging ◽  
Histological Analysis ◽  
Metatarsophalangeal Joint ◽  
Central Portion ◽  
Resonance Imaging ◽  
First Metatarsophalangeal Joint ◽  
Plantar Plate

Abstract Background There are discrepancies in the understanding of the structure of the capsuloligamentous complex of the first metatarsophalangeal joint (MTPJ); this study aims to investigate the differences with previous anatomical reports of high-resolution 3T magnetic resonance imaging (MRI) and histological analysis in illustrating the structure of the capsuloligamentous complex of the first MTPJ. Methods Nine fresh frozen cadaveric feet specimens (from two women and three men; aged 32 to 58 years) were used in this study. All specimens underwent MR examination with T1-weighted imaging and T2-weighted spectral attenuated inversion recovery in three planes. Subsequently, all cadaveric feet specimens were sliced into 2-mm-thick sections. The MRI features of the capsuloligamentous complex of the first MTPJ were analyzed in these specimens. Hematoxylin–eosin and Masson’s trichrome staining methods were used to explore the histologic features of the capsuloligamentous complex of the first MTPJ. Results Different from most previous studies, our results showed that the plantar plate could be divided into four portions including the central portion of the plantar plate, the intersesamoid, the sesamoid phalangeal and the metatarsosesamoid ligaments. The normal central portion of the plantar plate could be clearly visualized in the sagittal and coronal plane MR images. The intersesamoid ligament is a continuation of the central portion of the plantar plate on the sagittal plane on the gross specimen, the MR imaging, and the histological examination. On the coronal plane of the gross specimen and MR imaging, the sesamoid phalangeal ligaments and the central portion of the plantar plate can be seen as separate ligaments, but they appeared interwoven with the same continuous collagenous fibers on the histological analysis. Conclusion High-resolution 3T MRI allows accurate demonstration of the different anatomical details of the capsuloligamentous complex of the first MTPJ from previous anatomical reports. The histological analysis provides further understanding of the structures of the capsuloligamentous complex of the first MTPJ from previous studies.

Distortion in magnetic resonance images obtained for stereotactic localization

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 191-192 ◽  
Author(s):  
Lee Walton ◽  
Anna Hampshire ◽  
Paul Vaughan ◽  
David M. C. Forster ◽  
Andras A. Kemeny ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Three Dimensional ◽  
Magnetic Resonance Images ◽  
Side Plate ◽  
Content Type ◽  
Potential Source ◽  
Minimal Distortion ◽  
Source Of Error ◽  
Fine Print

✓ The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.

scholarly journals Effect of ependymal and pial surfaces on convectionenhanced delivery

2008 ◽  
Vol 109 (3) ◽  
pp. 547-552 ◽  
Author(s):  
Jay Jagannathan ◽  
Stuart Walbridge ◽  
John A. Butman ◽  
Edward H. Oldfield ◽  
Russell R. Lonser
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mr Imaging ◽  
Real Time ◽  
Drug Distribution ◽  
Leading Edge ◽  
Volume Of Distribution ◽  
Clinical Effects ◽  
Convection Enhanced Delivery ◽  
Pia Mater

Object Convection-enhanced delivery (CED) is increasingly used to investigate new treatments for central nervous system disorders. Although the properties of CED are well established in normal gray and white matter central nervous system structures, the effects on drug distribution imposed by ependymal and pial surfaces are not precisely defined. To determine the effect of these anatomical boundaries on CED, the authors infused low MW and high MW tracers for MR imaging near ependymal (periventricular) and pial (pericisternal) surfaces. Methods Five primates underwent CED of Gd-diethylenetriamine pentaacetic acid (Gd-DTPA; MW 590 D) or Gd-bound albumin (Gd-albumin; MW 72,000 D) during serial real-time MR imaging (FLAIR and T1-weighted sequences). Periventricular (caudate) infusions were performed unilaterally in 1 animal (volume of infusion [Vi] 57 μl) and bilaterally in 1 animal with Gd-DTPA (Vi = 40 μl on each side), and bilaterally in 1 animal with Gd-albumin (Vi = 80 μl on each side). Pericisternal infusions were performed in 2 animals with Gd-DTPA (Vi = 190 μl) or with Gd-albumin (Vi = 185 μl) (1 animal each). Clinical effects, MR imaging, and histology were analyzed. Results Large regions of the brain and brainstem were perfused with both tracers. Intraparenchymal distribution was successfully tracked in real time by using T1-weighted MR imaging. During infusion, the volume of distribution (Vd) increased linearly (R2 = 0.98) with periventricular (mean Vd/Vi ratio ± standard deviation; 4.5 ± 0.5) and pericisternal (5.2 ± 0.3) Vi, but did so only until the leading edge of distribution reached the ependymal or pial surfaces, respectively. After the infusate reached either surface, the Vd/Vi decreased significantly (ependyma 2.9 ± 0.8, pia mater 3.6 ± 1.0; p < 0.05) and infusate entry into the ventricular or cisternal cerebrospinal fluid (CSF) was identified on FLAIR but not on T1-weighted MR images. Conclusions Ependymal and pial boundaries are permeable to small and large molecules delivered interstitially by convection. Once infusate reaches these surfaces, a portion enters the adjacent ventricular or cisternal CSF and the tissue Vd/Vi ratio decreases. Although T1-weighted MR imaging is best for tracking intraparenchymal infusate distribution, FLAIR MR imaging is the most sensitive and accurate for detecting entry of Gd-labeled imaging compounds into CSF during CED.

Magnetic resonance appearance of multiple intracranial epidermoid cysts: intrathecal seeding of the cysts?

2000 ◽  
Vol 92 (4) ◽  
pp. 711-714 ◽  
Author(s):  
Yasushi Miyagi ◽  
Satoshi O. Suzuki ◽  
Toru Iwaki ◽  
Katsuya Ishido ◽  
Takehisa Araki ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Histological Analysis ◽  
Clinical Manifestations ◽  
Content Type ◽  
Epidermoid Cysts ◽  
Chronic Headaches ◽  
Cyst Rupture ◽  
Intracranial Epidermoid ◽  
Fine Print

✓ A 44-year-old man presented to the hospital with multiple intracranial epidermoid cysts. The clinical manifestations of his disease included chronic headaches and one seizurelike episode. Findings determined by magnetic resonance (MR) imaging, surgery, and histological analysis indicated intrathecal and intraventricular seeding of the cysts. Spontaneous (nontraumatic) seeding of multiple daughter cysts from intracranial epidermoid cysts is still very rare and their multiple appearances on MR imaging should be distinguished from the simple scattering of oily contents due to cyst rupture.

scholarly journals Peroneal and tibial intraneural ganglia: correlation between intraepineurial compartments observed on magnetic resonance images and the potential importance of these compartments

2007 ◽  
Vol 22 (6) ◽  
pp. 1-10 ◽  
Author(s):  
Robert J. Spinner ◽  
Kimberly K. Amrami ◽  
Diana Angius ◽  
Huan Wang ◽  
Stephen W. Carmichael
Keyword(s):  
Magnetic Resonance ◽  
Sciatic Nerve ◽  
Mr Imaging ◽  
Tibial Nerve ◽  
Cyst Formation ◽  
Magnetic Resonance Images ◽  
Imaging Features ◽  
Mr Images ◽  
Superior Tibiofibular Joint ◽  
Tibiofibular Joint

Object Previously the authors demonstrated that peroneal and tibial intraneural ganglia arising from the superior tibiofibular joint may occasionally extend proximally within the epineurium to reach the sciatic nerve. The dynamic nature of these cysts, dependent on intraarticular pressures, may give rise to differing clinical and imaging presentations that have remained unexplained until now. To identify the pathogenesis of these unusual cysts and to correlate their atypical magnetic resonance (MR) imaging appearance, the authors retrospectively reviewed their own experience as well as the published literature on these types of intraneural ganglia. Methods A careful review of MR images obtained in 22 patients with intraneural ganglia located about the knee region (18 peroneal and four tibial intraneural ganglia) allowed the authors to substantiate three different patterns: outer (epifascicular) epineurial (20 cases); inner (interfascicular) epineurial (one case); and combined outer and inner epineurial (one case). In these cases serial MR images allowed the investigators to track the movement of the cyst within the same layer of the epineurium. All lesions had connections to the superior tibiofibular joint. Nine patients were identified as having lesions with sciatic nerve extension. Seven patients harboring an outer epineurial cyst (six in whom the cyst involved the peroneal nerve and one in whom it involved the tibial nerve) had signs of sciatic nerve cross-over, with the cyst seen in the sciatic nerve and/or other terminal branches. In only two of these cases had the cyst previously been recognized to have sciatic nerve involvement. In contrast, in one case an inner epineurial cyst involving the tibial nerve ascended within the tibial division of the sciatic nerve and did not cross over. A single patient had a combination of both outer and inner epineurial cysts; these were easily distinguished by their distinctive imaging patterns. Conclusions This anatomical compartmentalization of intraneural cysts can be used to explain varied clinical and imaging patterns of cleavage planes for cyst formation and propagation. Compartmentalization elucidates the mechanism for cases of outer epineurial cysts in which there are primary ascent, sciatic cross-over, and descent of the lesion down terminal branches; correlates these cysts' atypical MR imaging features; and contrasts a different pattern of inner epineurial cysts in which ascent and descent occur without cross-over. The authors present data demonstrating that the dynamic phases of these intraneural ganglia frequently involve the sciatic nerve. Their imaging features are subtle and serve to explain the underrecognition and underreporting of the longitudinal extension of these cysts. Importantly, cysts extending to the sciatic nerve are still derived from the superior tibiofibular joint. Combined with the authors' previous experimental data, the current observations help the reader understand intraneural ganglia with a different, deeper degree of anatomical detail.

Canine model of convection-enhanced delivery of liposomes containing CPT-11 monitored with real-time magnetic resonance imaging

2008 ◽  
Vol 108 (5) ◽  
pp. 989-998 ◽  
Author(s):  
Peter J. Dickinson ◽  
Richard A. Lecouteur ◽  
Robert J. Higgins ◽  
John R. Bringas ◽  
Byron Roberts ◽  
...  
Keyword(s):  
Animal Model ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Real Time ◽  
Canine Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Convection Enhanced Delivery ◽  
Liposomal Nanoparticles ◽  
Volumes Of Distribution

Object Many factors relating to the safety and efficacy of convection-enhanced delivery (CED) into intracranial tumors are poorly understood. To investigate these factors further and establish a more clinically relevant large animal model, with the potential to investigate CED in large, spontaneous tumors, the authors developed a magnetic resonance (MR) imaging–compatible system for CED of liposomal nanoparticles into the canine brain, incorporating real-time MR imaging. Additionally any possible toxicity of liposomes containing Gd and the chemotherapeutic agent irinotecan (CPT-11) was assessed following direct intraparenchymal delivery. Methods Four healthy laboratory dogs were infused with liposomes containing Gd, rhodamine, or CPT-11. Convection-enhanced delivery was monitored in real time by sequential MR imaging, and the volumes of distribution were calculated from MR images and histological sections. Assessment of any toxicity was based on clinical and histopathological evaluation. Convection-enhanced delivery resulted in robust volumes of distribution in both gray and white matter, and real-time MR imaging allowed accurate calculation of volumes and pathways of distribution. Results Infusion variability was greatest in the gray matter, and was associated with leakage into ventricular or subarachnoid spaces. Complications were minimal and included mild transient proprioceptive deficits, focal hemorrhage in 1 dog, and focal, mild perivascular, nonsuppurative encephalitis in 1 dog. Conclusions Convection-enhanced delivery of liposomal Gd/CPT-11 is associated with minimal adverse effects in a large animal model, and further assessment for use in clinical patients is warranted. Future studies investigating real-time monitored CED in spontaneous gliomas in canines are feasible and will provide a unique, clinically relevant large animal translational model for testing this and other therapeutic strategies.

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