Marko Kangasniemi

MRI-guided thermal therapy of transplanted tumors in the canine prostate using a directional transurethral ultrasound applicator

To evaluate MRI‐based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model.

Interleaved echo-planar imaging for fast multiplanar magnetic resonance temperature imaging of ultrasound thermal ablation therapy

To develop a multiplanar magnetic resonance temperature imaging (MRTI) technique based on interleaved gradient‐echo echo‐planar imaging (EPI), verify in phantom, develop software tools to process and display data on a clinical scanner in near real‐time, and demonstrate feasibility to monitor ultrasound thermal ablation therapy in vivo.

Multiplanar MR temperature-sensitive imaging of cerebral thermal treatment using interstitial ultrasound applicators in a canine model

To study the feasibility of an interleaved gradient‐echo, echo‐planar imaging (iGE‐EPI) sequence for multiplanar magnetic resonance temperature imaging (MRTI) to monitor intracerebral thermal treatment three‐dimensionally using multielement ultrasound applicators.

Technical developments for cerebral thermal treatment: Water-cooled diffusing laser fibre tips and temperature-sensitive MRI using intersecting image planes

The aim was to determine if water-cooled diffusing tips could produce larger and safer (better controlled) thermal lesions than non-cooled diffusing tips at 980 nm. Thermal lesions were induced in beef myocardium in vitro with and without water cooling using a 980 nm diode laser at various power levels. Seven intracerebral treatments were performed in six canines using water-cooled diffusing tips with four animals having intracerebral transmissible venereal tumours grown from inoculate. Magnetic resonance thermal imaging (MRTI)-based feedback software using a fast, radio frequency-spoiled gradient echo acquisition with two intersecting image planes was used for on-line monitoring and control of treatment and for the evaluation of in vivo laser lesion production. In cases where two-plane MRTI was employed, the maximum calculated temperature was compared in each plane. Using water-cooled tips and 400 µm core diameter laser diffusing fibres in in vitro beef myocardium, power of up to 9.5 W was applied for 8 min without tip failure. Without cooling, tip failure occurred in under 4 min at 6 W, in under 2 min at 7 W and instantaneously at 8 W. Additionally, char accompanied lesions made with uncooled tips while cooled application resulted in only minimal char at only the highest thermal dose. Achieved lesion cross-sectional diameters in in vitro samples were up to 26.5 × 23.3 mm when water cooling was used. In canine brain and transmissible venereal tumours, up to 18.1 × 21.4 mm lesions were achieved. It is concluded that water cooling allows safe application of higher power to small core diameter diffusing tip fibres, which results in larger thermal lesions than can be achieved without cooling. Two-plane MRTI enhances on-line monitoring and feedback of thermal treatment.

Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors

Kangasniemi M, Stafford RJ, Price RE, et al. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors. Invest Radiol 2003;38:102–107. Rationale and Objectives.Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Materials and Methods.Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Results.Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Conclusion.Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

Hormone pretreatment enhances recovery of spermatogenesis in rats after neutron irradiation.

Previous studies showed that a 6-week pretreatment of rats with testosterone plus estradiol enhanced the recovery of spermatogenesis 9 weeks after gamma irradiation, resulting in a dose-modifying factor (DMF) of about 2. To test whether the effect of the hormone treatment was mediated through changes in oxygen tension, thiol levels or DNA repair, we irradiated the testes of rats with neutrons, which depend less on these factors than does low-LET radiation for their cytotoxic action. Control rats and rats treated with testosterone plus estradiol were irradiated with 0.7-2.7 Gy of cyclotron-generated high-energy neutrons. The recovery of spermatogenesis was assessed 9 weeks after irradiation by testis weights, sperm counts and the tubule repopulation indices. Greater recovery of spermatogenesis was observed for all end points, with a DMF of about 2 for rats treated with testosterone plus estradiol compared to the irradiated, cholesterol-treated rats. The equal protection factors for neutrons and gamma rays indicate that oxygen, thiols and repair of DNA damage are unlikely to be involved in the protective effect of the hormone treatment.

Hormonal Protection of Spermatogenic Stem Cells Against Cytotoxic Agents

Various cytotoxic agents, including radiation and several chemotherapeutic drugs, produce prolonged depression of spermatogenesis in rodents and humans (1–3). However, pretreatment of rats with hormones that suppress intratesticular levels of testosterone and the completion of spermatogenesis enhances the recovery of spermatogenesis from stem cells after the cytotoxic insult (4). Although most studies of hormonal protection have employed the chemotherapeutic drug procarbazine as the cytotoxic agent, protection has also been shown following cyclophosphamide (5) and gamma irradiation (6). It had generally been assumed that the protection of spermatogenic function was a result of protecting the stem spermatogonia against killing, although alternative mechanisms such as enhancement of the number of stem cells at the time of cytotoxic treatment or of their recovery following such treatments have also been suggested (7–9).

Computer-controlled production of intracranial lesions using magnetic resonance thermometry

Fiber optically delivered laser energy may be ideal in treating small intracerebral lesions with minimal invasiveness. We have continued development of a laser-computer system for automated magnetic resonance thermal imaging (MRTI) guidance and control of intracerebral laser interstitial thermal therapy (LITT). The system consists of a workstation which is interfaced to a clinical MR scanner via Ethernet and to a compact high power diode laser via hardware interface. The system analyzes MRTI data to compute temperature changes based on the proton resonance frequency (PRF) shift, and constructs two-dimensional maps of temperature and estimated chronic thermal damage during therapy. Images are obtained approximately every 4.5 seconds allowing near-real-time tracking of LITT progress. A graphical user interface allows specification of temperature constraints on the image which regulate delivery of thermal energy. We have tested the ability of the system to create small focal intracranial lesions of specified dimension in both normal canine brain (n = 6 animals, 15 lesions) and in an intracerebral tumor model grown from inoculum (n = 11 animals, 15 lesions). Histological analysis was used to assess the accuracy of MRTI-derived predictions of lesion size and to assess effectiveness of reaching prescribed tumor boundaries.