Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T.

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.

Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat

Purpose. Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. Methods. We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. Results. Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. Conclusions. In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease (AU)

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Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat.

PURPOSE: Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. METHODS: We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. RESULTS: Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. CONCLUSIONS: In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease.

Scintigraphic comparison of intra-arterial injection and distal intravenous regional limb perfusion for administration of mesenchymal stem cells to the equine foot.

REASONS FOR PERFORMING STUDY: Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use. OBJECTIVES: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v. RLP through the lateral palmar digital vein. STUDY DESIGN: In vivo experimental study. METHODS: (99m) Tc-HMPAO-labelled MSCs were injected through the median artery of one limb and the lateral palmar digital vein of the other limb of 6 horses under general anaesthesia. No tourniquet was used for the i.a. injection. A pneumatic tourniquet was placed on the metacarpus for i.v. injection. Scintigraphic images were obtained up to 24 h after injection. RESULTS: Intra-arterial injection resulted in MSCs retention within the limb despite the absence of a tourniquet and no thrombosis was observed. Both i.a. injection and i.v. RLP led to distribution of MSCs to the foot. The i.a. injection resulted in a more homogeneous distribution. The MSC uptake was higher with i.v. RLP at the initial timepoints, but no significant difference was present at 24 h. CONCLUSIONS: Both i.a. injection through the median artery without a tourniquet and i.v. RLP performed through the lateral palmar digital vein under general anaesthesia are safe and reliable methods for administration of MSCs to the equine foot. The i.a. technique is preferred owing to the better distribution, but is technically more challenging. The feasibility of performing these techniques on standing horses remains to be investigated.

Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.

REASONS FOR PERFORMING STUDY: Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required. OBJECTIVES: We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries. STUDY DESIGN: In vivo experimental study. METHODS: Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h. RESULTS: Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse. CONCLUSIONS AND POTENTIAL RELEVANCE: Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.

Scintigraphic evaluation of intra-arterial and intravenous regional limb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal limb using (99m) Tc-HMPAO.

REASONS FOR PERFORMING STUDY: Mesenchymal stem cells (MSCs) are commonly injected intralesionally for treatment of soft tissue injuries in the horse. Alternative routes of administration would be beneficial for treatment of lesions that cannot be accessed directly or to limit needle-induced iatrogenic damage to the surrounding tissue. OBJECTIVES: The purpose of our study was to evaluate MSC distribution after intra-arterial (IA) and intravenous (IV) regional limb perfusions (RLP) using scintigraphy. We hypothesised that MSCs would persist in the distal limb after tourniquet removal and that both techniques would lead to diffuse MSC distribution. METHODS: Six horses were used in the study. MSCs were labelled with hexamethyl propylene amine oxime (HMPAO) and technetium-99m. RLP was performed through the median artery of one forelimb and the cephalic vein of the opposite limb under general anaesthesia. The tourniquet was left in place for 45 min. Scintigraphic images were obtained at 0, 45, 75 min, 6 h and 24 h post injection. RESULTS: Distribution of labelled MSCs through the entire distal limb was achieved with all 6 IA RLP, but 3 out of 6 IV RLP showed poor or absent uptake distal to the metacarpus. Mesenchymal stem cell persistence was 39% (30-60%) and 28% (14-50%) (median [minimum-maximum]) at 6 h for IA and IV RLP, respectively. Severe arterial thrombosis occurred in one horse after IA RLP. CONCLUSIONS: Both IA and IV RLP of the distal limb result in MSC persistence in perfused tissues. The IA perfusion resulted in more reliable cell distribution to the pastern and foot area. POTENTIAL RELEVANCE: Regional limb perfusion of MSCs might be used in cases where intralesional injection is not possible or in order to avoid iatrogenic needle damage. Further work is needed to assess the safety of IA RLP before its clinical use.

Tick infestation and spotted-fever group Rickettsia in shelter dogs, California, 2009.

In response to an outbreak of Rocky Mountain spotted fever (RMSF) in Baja California in early 2009, dogs at two shelters in neighbouring Imperial County, California, were evaluated for ectoparasites. Brown dog ticks (Rhipicephalus sanguineus), a recognized vector for RMSF, were found on 35 (30%) of 116 dogs but all ticks tested negative for Rickettsia rickettsii by PCR.

Effect of prescribed fire for tick control in California chaparral.

Prescribed fire was investigated as a method for controlling ixodid and argasid ticks in chaparral habitats in northern California. Two experimental and two adjacent control plots within a wildlife preserve were monitored for 1 yr postburn. Ticks were collected by flagging vegetation, by CO2-baited pitfall trap, and by live-trapping rodents. Twice as many rodents were caught at control sites compared with burn sites and no dusky-footed woodrats, Neotoma fuscipes Baird, were found in the treatment sites postburn. This species is known to be a reservoir of the agents of Lyme disease, Borrelia burgdorferi sensu stricto Johnson, Schmid, Hyde, Steigerwalt & Brenner, and human granulocytic anaplasmosis, Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, Rurangirwa. Six ixodid tick species were removed from rodents (Ixodes pacificus Cooley & Kohls, Ixodes jellisoni Cooley & Kohls, Ixodes spinipalpis Hadwen & Nuttall, Ixodes woodi Bishopp, Dermacentor occidentalis Marx, and Dermacentor parumapertus Neumann), two of which transmit bacterial zoonotic agents to people in the far-western United States. There was no decrease in number of ticks per animal trapped at either burn site compared with controls; in fact, the mean number of immature I. pacificus per rodent was significantly higher at one burn site than its control site. Soil refugia may protect ticks from fire-induced mortality; the argasid tick Ornithodoros coriaceus Koch, which lives in soil, was unaffected by the prescribed fire as were I. pacificus and D. occidentalis buried in packets 2.5 cm below ground. We conclude that although prescribed fires in chaparral habitats may diminish local rodent abundance, it does not decrease tick loads on rodents. Furthermore, burning chaparral does not result in a decreased abundance of adult ixodid ticks on vegetation and apparently does not affect argasid or ixodid ticks that are sheltered within soil refugia.

Alpha-II-spectrin after controlled cortical impact in the immature rat brain.

Proteolytic processing plays an important role in regulating a wide range of important cellular functions, including processing of cytoskeletal proteins. Loss of cytoskeletal proteins such as spectrin is an important characteristic in a variety of acute central nervous system injuries including ischemia, spinal cord injury and traumatic brain injury (TBI). The literature contains extensive information on the proteolytic degradation of alpha-II-spectrin after TBI in the adult brain. By contrast, there is limited knowledge on the characteristics and relevance of these important processes in the immature brain. The present experiments examine TBI-induced proteolytic processing of alpha-II-spectrin after TBI in the immature rat brain. Distinct proteolytic products resulting from the degradation of the cytoskeletal protein alpha-II-spectrin by calpain and caspase 3 were readily detectable in cortical brain parenchyma and cerebrospinal fluid after TBI in immature rats.