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2.
Int J Hyperthermia ; 37(1): 1052-1059, 2020.
Article in English | MEDLINE | ID: mdl-32892667

ABSTRACT

PURPOSE: When doxorubicin (DOX) is administered via lyso-thermosensitive liposomes (LTLD), mild hyperthermia enhances localized delivery to heated vs. unheated tumors. The optimal LTLD dose and the impact of different doses on systemic drug distribution are unknown.Materials and methods: In this study, we evaluated local and systemic DOX delivery with three LTLD doses (0.1, 0.5, and 2.5 mg/kg) in a Vx2 rabbit tumor model. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the intended heating duration (40 min).Results: DOX concentration in tissues delivered from LTLD combined with MR-HIFU mild hyperthermia are dose-dependent, including heated/unheated tumor, heart, and other healthy organs. Higher DOX accumulation and tumor-to-heart drug concentration ratio, defined as the ratio of DOX delivered into the tumor vs the heart, were observed in heated tumors compared to unheated tumors in all three tested doses. The DOX uptake efficiency for each mg/kg of LTLD injected IV of heated tumor was significantly higher than that of unheated tumor and heart within the tested dose range (0.1-2.5 mg/kg). The DOX uptake for the heart linearly scaled up as a function of dose while that for the heated tumor showed some evidence of saturation at the high dose of 2.5 mg/kg.Conclusions: These results provide guidance on clinical protocol design of hyperthermia-triggered drug delivery.


Subject(s)
Hyperthermia, Induced , Neoplasms , Animals , Antibiotics, Antineoplastic/therapeutic use , Doxorubicin/therapeutic use , Drug Delivery Systems , Hyperthermia , Liposomes , Neoplasms/therapy , Rabbits
4.
Int J Hyperthermia ; 36(1): 1084-1097, 2019.
Article in English | MEDLINE | ID: mdl-31707872

ABSTRACT

Background: The use of magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) to deliver mild hyperthermia requires stable temperature mapping for long durations. This study evaluates the effects of respiratory motion on MR thermometry precision in pediatric subjects and determines the in vivo feasibility of circumventing breathing-related motion artifacts by delivering MR thermometry-controlled HIFU mild hyperthermia during repeated forced breath holds.Materials and methods: Clinical and preclinical studies were conducted. Clinical studies were conducted without breath-holds. In phantoms, breathing motion was simulated by moving an aluminum block towards the phantom along a sinusoidal trajectory using an MR-compatible motion platform. In vivo experiments were performed in ventilated pigs. MR thermometry accuracy and stability were evaluated.Results: Clinical data confirmed acceptable MR thermometry accuracy (0.12-0.44 °C) in extremity tumors, but not in the tumors in the chest/spine and pelvis. In phantom studies, MR thermometry accuracy and stability improved to 0.37 ± 0.08 and 0.55 ± 0.18 °C during simulated breath-holds. In vivo MR thermometry accuracy and stability in porcine back muscle improved to 0.64 ± 0.22 and 0.71 ± 0.25 °C during breath-holds. MR-HIFU hyperthermia delivered during intermittent forced breath holds over 10 min duration heated an 18-mm diameter target region above 41 °C for 10.0 ± 1.0 min, without significant overheating. For a 10-min mild hyperthermia treatment, an optimal treatment effect (TIR > 9 min) could be achieved when combining 36-60 s periods of forced apnea with 60-155.5 s free-breathing.Conclusion: MR-HIFU delivery during forced breath holds enables stable control of mild hyperthermia in targets adjacent to moving anatomical structures.


Subject(s)
Breath Holding , High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Animals , Feasibility Studies , Female , Swine
5.
J Craniofac Surg ; 30(8): 2432-2438, 2019.
Article in English | MEDLINE | ID: mdl-31306379

ABSTRACT

Actinomycosis is a rare disease that remains difficult to diagnose and manage. Prompted by 2 recent cases the authors sought evidence-based conclusions about best practice. A systematic review was conducted using standard PRISMA methodology. The study was registered prospectively (PROSPERO: CRD42018115064). Thirty-three children from 23 series are described. The mean age was 8 years (range 3-17). Fifty-five percent were female. Twenty cases involved bone (usually mandible); 13 cases involved cervicofacial soft tissue. Poor dental hygiene and oral trauma were implicated. The median diagnostic delay was 12 weeks (range 1-156 weeks). The median duration of definitive antibiotic therapy was 17 weeks (range 1-130 weeks). Although diagnostic delay did not correlate with number of surgeries, bony involvement was associated with more procedures (P = 0.008, unpaired t test). All (6) cases with residual infection had bony involvement (P = 0.06, Fisher exact test). Neither diagnostic delay nor number of surgeries significantly influenced infection-free outcome which, instead, relies on aggressive surgical debridement and prolonged antibiotic therapy. Mandibular involvement exhibits a higher surgical burden and chronicity in around a third of cases. As dental caries are implicated in mandibular disease, preventative strategies must focus on improving pediatric oral hygiene.


Subject(s)
Actinomycosis, Cervicofacial/diagnosis , Actinomycosis, Cervicofacial/therapy , Adolescent , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Debridement , Delayed Diagnosis , Disease Progression , Female , Humans , Male , Mandible
6.
Plast Reconstr Surg ; 143(3): 698-699, 2019 03.
Article in English | MEDLINE | ID: mdl-30817641

ABSTRACT

Reconstruction of the nipple-areola complex is the culmination of a long road for patients who have suffered breast cancer. The postoperative dressing of the reconstructive nipple must protect it from mechanical forces, trauma, and infection. A broad array of dressings has been used for the reconstructed nipple. The authors propose the use of a readily available adhesive eye protector as a simple and cost-effective dressing for the reconstructed nipple-areola complex.


Subject(s)
Bandages , Breast Neoplasms/surgery , Mammaplasty/methods , Nipples/surgery , Protective Devices , Adhesives , Female , Humans , Mastectomy/adverse effects , Postoperative Care/instrumentation
7.
Aesthet Surg J ; 39(12): 1309-1318, 2019 11 13.
Article in English | MEDLINE | ID: mdl-30380010

ABSTRACT

Rhinoplasty utilizes cartilage harvested from the nasal septum as autologous graft material. Traditional dogma espouses preservation of the "L-strut" of dorsal and caudal septum, which is less resistant to axial loading than virgin septum. Considering the 90° angle between dorsal and caudal limbs, the traditional L-strut also suffers from localized increases in internal stresses leading to premature septal "cracking," structural-scale deformation, or both. Deformation and failure of the L-strut leads to nasal deviation, saddle deformity, loss of tip support, or restriction of the nasal valve. The balance between cartilage yield and structural integrity is a topographical optimization problem. Guided by finite element (FE) modelling, recent efforts have yielded important modifications including the chamfering of right-angled corners to reduce stress concentrations and the preservation of a minimum width along the inferior portion of the caudal strut. However, all existing FE studies offer simplified assumptions to make the construct easier to model. This review article highlights advances in our understanding of septal engineering and identifies areas that require more work to further refine the balance between the competing interests of graft acquisition and the maintenance of nasal structural integrity.


Subject(s)
Models, Theoretical , Nasal Cartilages/surgery , Rhinoplasty/methods , Autografts , Biomechanical Phenomena , Finite Element Analysis , Humans , Nasal Septum/surgery
8.
Int J Hyperthermia ; 36(1): 196-203, 2019.
Article in English | MEDLINE | ID: mdl-30541350

ABSTRACT

Thermosensitive liposomal doxorubicin (LTSL-Dox) combined with mild hyperthermia enhances the localized delivery of doxorubicin (Dox) within a heated region. The optimal heating duration and the impact of extended heating on systemic drug distribution are unknown. Here we evaluated local and systemic Dox delivery with two different mild hyperthermia durations (42 °C for 10 or 40 minutes) in a Vx2 rabbit tumor model. We hypothesized that longer duration of hyperthermia would increase Dox concentration in heated tumors without increasing systemic exposure. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the prescribed heating durations. Forty-minutes of heating resulted in a nearly 6-fold increase in doxorubicin concentration in heated vs unheated tumors in the same animals. Therapeutic ratio, defined as the ratio of Dox delivered into the heated tumor vs the heart, increased from 1.9-fold with 10 minutes heating to 4.4-fold with 40 minutes heating. MR-HIFU can be used to guide, deliver and monitor mild hyperthermia of a Vx2 tumor model in a rabbit model, and an increased duration of heating leads to higher Dox deposition from LTSL-Dox in a target tumor without a concomitant increase in systemic exposure. Results from this preclinical study can be used to help establish clinical treatment protocols for hyperthermia mediated drug delivery.


Subject(s)
Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use , Heating/methods , High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Animals , Doxorubicin/pharmacology , Female , Humans , Polyethylene Glycols/pharmacology , Polyethylene Glycols/therapeutic use , Rabbits
9.
NPJ Regen Med ; 3: 13, 2018.
Article in English | MEDLINE | ID: mdl-30155273

ABSTRACT

The recent prolonged conflicts in Iraq and Afghanistan saw the advancement of deployed trauma care to a point never before seen in war. The rapid translation of lessons from combat casualty care research, facilitated by an appetite for risk, contributed to year-on-year improvements in care of the injured. These paradigms, however, can only ever halt the progression of damage. Regenerative medicine approaches, in contrast, hold a truly disruptive potential to go beyond the cessation of damage from blast or ballistic trauma, to stimulate its reversal, and to do so from a very early point following injury. The internationally distributed and, in parts austere environments in which operational medical care is delivered provide an almost unique challenge to the development and translation of regenerative medicine technologies. In parallel, however, an inherent appetite for risk means that Defence will always be an early adopter. In focusing our operational priorities for regenerative medicine, the authors conducted a review of the current research landscape in the UK and abroad and sought wide clinical opinion. Our priorities are all applicable very far forward in the patient care pathway, and are focused on three broad and currently under-researched areas, namely: (a) blood, as an engineered tissue; (b) the mechanobiology of deep tissue loss and mechanobiological approaches to regeneration, and; (c) modification of the endogenous response. In focusing on these areas, we hope to engender the development of regenerative solutions for improved functional recovery from injuries sustained in conflict.

11.
J Magn Reson Imaging ; 46(2): 354-364, 2017 08.
Article in English | MEDLINE | ID: mdl-28067975

ABSTRACT

PURPOSE: To evaluate magnetization-prepared 3D T2 -weighted magnetic resonance imaging (MRI) measurements of acute tissue changes produced during ablative MR high-intensity focused ultrasound (MR-HIFU) exposures. MATERIALS AND METHODS: A clinical MR-HIFU system (3T) was used to generate thermal lesions (n = 24) in the skeletal muscles of three pigs. T1 -weighted, 2D T2 -weighted, and magnetization-prepared 3D T2 -weighted sequences were acquired before and after therapy to evaluate tissue changes following ablation. Tissues were harvested shortly after imaging, fixed in formalin, and gross-sectioned. Select lesions were processed into whole-mount sections. Lesion dimensions for each imaging sequence (length, width) and for gross sections (diameter of lesion core and rim) were assessed by three physicists. Contrast-to-background ratio between lesions and surrounding muscle was compared. RESULTS: Lesion dimensions on T1 and 2D T2 -weighted imaging sequences were well correlated (R2 ∼0.7). The contrast-to-background ratio between lesion and surrounding muscle was 7.4 ± 2.4 for the magnetization-prepared sequence versus 1.7 ± 0.5 for a conventional 2D T2 -weighted acquisition, and 7.0 ± 2.9 for a contrast-enhanced T1 -weighted sequence. Compared with diameter measured on gross pathology, all imaging sequences overestimated the lesion core by 22-33%, and underestimated the lesion rim by 6-13%. CONCLUSION: After MR-HIFU exposures, measurements of the acute thermal damage patterns in muscle using a magnetization-prepared 3D T2 -weighted imaging sequence correlate with 2D T2 -weighted and contrast-enhanced T1 -weighted imaging, and all agree well with histology. The magnetization-prepared sequence offers positive tissue contrast and does not require IV contrast agents, and may provide a noninvasive imaging evaluation of the region of acute thermal injury at multiple times during HIFU procedures. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:354-364.


Subject(s)
Extracorporeal Shockwave Therapy , Magnetic Resonance Imaging , Muscle, Skeletal/diagnostic imaging , Animals , Catheterization , Contrast Media , Female , Hot Temperature , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Necrosis , Oxygen , Signal-To-Noise Ratio , Swine
12.
J R Army Med Corps ; 163(1): 58-64, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27278968

ABSTRACT

AIMS: While the epidemiology of amputations in patients with burns has been investigated previously, the effect of an amputation on burn size and its impact on fluid management have not been considered in the literature. Fluid resuscitation volumes are based on the percentage of the total body surface area (%TBSA) burned calculated during the primary survey. There is currently no consensus as to whether the fluid volumes should be recalculated after an amputation to compensate for the new body surface area. The aim of this study was to model the impact of an amputation on burn size and predicted fluid requirement. METHODS: A retrospective search was performed of the database at the Queen Elizabeth Hospital Birmingham Regional Burns Centre to identify all patients who had required an early amputation as a result of their burn injury. The search identified 10 patients over a 3-year period. Burn injuries were then mapped using 3D modelling software. BurnCase3D is a computer program that allows accurate plotting of burn injuries on a digital mannequin adjusted for height and weight. Theoretical fluid requirements were then calculated using the Parkland formula for the first 24 h, and Herndon formula for the second 24 h, taking into consideration the effects of the amputation on residual burn size. RESULTS AND CONCLUSIONS: This study demonstrated that amputation can have an unpredictable effect on burn size that results in a significant deviation from predicted fluid resuscitation volumes. This discrepancy in fluid estimation may cause iatrogenic complications due to over-resuscitation in burn-injured casualties. Combining a more accurate estimation of postamputation burn size with goal-directed fluid therapy during the resuscitation phase should enable burn care teams to optimise patient outcomes.


Subject(s)
Algorithms , Amputation, Surgical , Body Surface Area , Burns/therapy , Fluid Therapy , Resuscitation , Adolescent , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
13.
Tissue Eng Part B Rev ; 23(2): 183-198, 2017 04.
Article in English | MEDLINE | ID: mdl-27824295

ABSTRACT

Traumatic soft tissue wounds present a significant reconstructive challenge. The adoption of closed-circuit negative pressure wound therapy (NPWT) has enabled surgeons to temporize these wounds before reconstruction. Such systems use porous synthetic foam scaffolds as wound fillers at the interface between the negative pressure system and the wound bed. The idea of using a bespoke porous biomaterial that enhances wound healing, as filler for an NPWT system, is attractive as it circumvents concerns regarding reconstructive delay and the need for dressing changes that are features of the current systems. Porous foam biomaterials are mechanically robust and able to synthesize in situ. Hence, they exhibit potential to fulfill the niche for such a functionalized injectable material. Injectable scaffolds are currently in use for minimally invasive surgery, but the design parameters for large-volume expansive foams remain unclear. Potential platforms include hydrogel systems, (particularly superabsorbent, superporous, and nanocomposite systems), polyurethane-based moisture-cured foams, and high internal phase emulsion polymer systems. The aim of this review is to discuss the design parameters for such future biomaterials and review potential candidate materials for further research into this up and coming field.


Subject(s)
Hydrogels/pharmacology , Injections , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Wound Healing/drug effects , Animals , Biomechanical Phenomena/drug effects , Humans , Porosity
14.
Ann Med Surg (Lond) ; 9: 41-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27408713

ABSTRACT

INTRODUCTION: Male breast cancer is extremely rare with an incidence of less than 1% of all breast cancers. Literature reports a peak of incidence at roughly 71 years of age. Management currently follows the same clinical pathways as female breast cancer as a general rule. METHODS: A retrospective search for all patients who were referred and diagnosed with male breast cancer at our centre was undertaken. Patients notes were then explored for demographics, histological staging, multidisciplinary team meeting outcome and treatment. A literature search including the search terms 'Male Breast Cancer AND Surgery' or 'Male Breast Cancer AND Experience' were used. Non English language articles, or those without abstracts were excluded. RESULTS: Seven patients were reviewed over 3 years (2006-2009). Mean agea was 69 years and mean lesion size was 15 mm. Histology was invasive ductal carcinoma for all patients. All patients were ER receptor positive. Two patients were HER2 positive. Five patients were offered mastectomy. One patient refused treatment. In follow up at 36 months there were 3 recurrences. 1 patient was lost to follow up. There were 3 mortalities. The literature search identified 72 articles. Articles were subdivided into those that discussed the surgical management of male breast cancer (n = 8), articles that discussed male breast cancer as podium presentations or posters with no full text article publication (n = 13) and finally full text publications of case experience of male breast cancer (n = 21). DISCUSSION: We report a series of seven cases of male breast cancer encountered over three years, evaluating patient demographics as well as treatment and outcomes. In our series patients were managed with mastectomy. New evidence is questioning the role of mastectomy against breast conserving surgery in male patients. Furthermore there is a lack of reporting infrastructure for national data capture of the benefits of surgical modalities. Literature review highlights the varied clinical experience between units that remains reported as podium presentation but not published. The establishment of an online international reporting registry would allow for efficient analysis of surgical outcomes to improve patient care from smaller single centres. This would facilitate large scale meta analysis by larger academic surgical centres.

15.
Int J Radiat Oncol Biol Phys ; 95(4): 1259-67, 2016 07 15.
Article in English | MEDLINE | ID: mdl-27209510

ABSTRACT

PURPOSE: To evaluate the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. METHODS AND MATERIALS: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. RESULTS: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. CONCLUSIONS: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.


Subject(s)
High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Neoplasm Recurrence, Local/therapy , Rectal Neoplasms/therapy , Animals , Humans , Neoplasm Recurrence, Local/diagnostic imaging , Rectal Neoplasms/diagnostic imaging , Swine , Thermometry
16.
Int J Hyperthermia ; 32(6): 673-87, 2016 09.
Article in English | MEDLINE | ID: mdl-27210733

ABSTRACT

UNLABELLED: There is growing interest in performing hyperthermia treatments with clinical magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) therapy systems designed for tissue ablation. During hyperthermia treatment, however, due to the narrow therapeutic window (41-45 °C), careful evaluation of the accuracy of proton resonant frequency (PRF) shift MR thermometry for these types of exposures is required. PURPOSE: The purpose of this study was to evaluate the accuracy of MR thermometry using a clinical MR-HIFU system equipped with a hyperthermia treatment algorithm. METHODS: Mild heating was performed in a tissue-mimicking phantom with implanted temperature sensors using the clinical MR-HIFU system. The influence of image-acquisition settings and post-acquisition correction algorithms on the accuracy of temperature measurements was investigated. The ability to achieve uniform heating for up to 40 min was evaluated in rabbit experiments. RESULTS: Automatic centre-frequency adjustments prior to image-acquisition corrected the image-shifts in the order of 0.1 mm/min. Zero- and first-order phase variations were observed over time, supporting the use of a combined drift correction algorithm. The temperature accuracy achieved using both centre-frequency adjustment and the combined drift correction algorithm was 0.57° ± 0.58 °C in the heated region and 0.54° ± 0.42 °C in the unheated region. CONCLUSION: Accurate temperature monitoring of hyperthermia exposures using PRF shift MR thermometry is possible through careful implementation of image-acquisition settings and drift correction algorithms. For the evaluated clinical MR-HIFU system, centre-frequency adjustment eliminated image shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Hyperthermia, Induced , Animals , Female , Magnetic Resonance Imaging , Neoplasms/diagnostic imaging , Neoplasms/surgery , Neoplasms/therapy , Rabbits , Thermometry
17.
J Trauma Acute Care Surg ; 81(2): 380-7, 2016 08.
Article in English | MEDLINE | ID: mdl-27192464

ABSTRACT

BACKGROUND: Decompressing an acute lower extremity compartment syndrome salvages muscle and nerve and preserves limb function. However, reperfusion of ischemic tissue causes a systemic insult that can be life threatening. Hence, the management of missed acute lower limb compartment syndrome remains controversial. The aim of this study was to evaluate the literature and, together with our own experience from a Level 1 trauma center, clarify the management of missed compartment syndrome in the physiologically stable patient. METHODS: Pubmed, EMBASE, MEDLINE, the Cochrane database of systematic reviews and the Cochrane central register of controlled trials were searched. Studies were evaluated using the GRADE methodology. In addition, our trauma database was searched (2005 to May 2015) for additional cases, and a multidisciplinary case note review was conducted for all cases identified. This study was registered prospectively on the PROSPERO database (CRD42015026098). RESULTS: Our systematic review yielded 9 studies, including one case-controlled study, 3 case series, and 5 case reports with a total of 57 patients and 64 limbs. Overall, study quality was "very low" with the exception of the case-controlled study, which was "low." Delayed compartment decompression (6-120 hours) resulted in amputation rates of 5 of 24, 8 of 19, 4 of 5, and 2 of 3 limbs. Two patients died of complications associated with late compartment decompression. One compartment syndrome of the buttock was managed nonoperatively. Most surviving limbs exhibited functional deficits.Additionally, our experience comprised 10 cases. Of the six who underwent compartment decompression, the burden of subsequent morbidity included three amputations (one above knee), two complete foot drops, and one episode of severe sepsis. As this experience mirrored the poor outcomes reported in the literature, we managed the four most recent cases nonoperatively. All remain ambulant with incomplete foot drops or limb weakness. CONCLUSION: Surgical decompression of missed acute lower limb compartment syndrome yields an early physiological insult and a high late-amputation rate. Managing selected cases nonoperatively may result in less early morbidity and yield superior long-term results, but the evidence remains sparse and of poor quality. LEVEL OF EVIDENCE: Systematic review, level III.


Subject(s)
Compartment Syndromes/diagnosis , Compartment Syndromes/surgery , Diagnostic Errors , Lower Extremity/injuries , Decompression, Surgical , Humans , Trauma Centers
18.
Pediatr Blood Cancer ; 63(10): 1753-60, 2016 10.
Article in English | MEDLINE | ID: mdl-27199087

ABSTRACT

BACKGROUND: Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. PROCEDURE: Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. RESULTS: Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. CONCLUSIONS: Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors.


Subject(s)
High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging , Sarcoma/therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Movement , Sarcoma/diagnostic imaging , Sarcoma/pathology
19.
PLoS One ; 10(12): e0144742, 2015.
Article in English | MEDLINE | ID: mdl-26659073

ABSTRACT

PURPOSE: Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. METHODS: Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. RESULTS: All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. CONCLUSION: Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.


Subject(s)
High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Neuralgia/surgery , Neuroimaging/methods , Peripheral Nerves/surgery , Animals , Disease Models, Animal , Female , Hindlimb/innervation , Histocytochemistry , Magnetic Resonance Imaging/instrumentation , Neuralgia/pathology , Neuralgia/physiopathology , Pilot Projects , Swine , Temperature , Ultrasonic Waves
20.
Int J Hyperthermia ; 31(2): 163-81, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25753369

ABSTRACT

In this review we present the current status of ultrasound thermometry and ablation monitoring, with emphasis on the diverse approaches published in the literature and with an eye on which methods are closest to clinical reality. It is hoped that this review will serve as a guide to the expansion of sonographic methods for treatment monitoring and thermometry since the last brief review in 2007.


Subject(s)
Hyperthermia, Induced/methods , Ultrasonic Therapy , Body Temperature , Humans , Thermometry/methods
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