X
|
STUDENT DIGITAL NEWSLETTER ALAGAPPA INSTITUTIONS |
|
Robert O?onnor, MD, MPH
Considering these latter risks and equivocal data from clinical trials 1026 to date erectile dysfunction drugs without side effects generic 100mg aurogra, hypothermia should continue to be considered an investigational treatment erectile dysfunction drugs non prescription generic 100 mg aurogra with visa. Pentobarbital is the most commonly used barbiturate for this indication erectile dysfunction and zantac order aurogra 100 mg with amex, although thiopental also has been used drugs used for erectile dysfunction generic 100 mg aurogra with mastercard. Pentobarbital should be administered as an intravenous loading infusion totaling 25 mg/kg. Side effects associated with high-dose barbiturate therapy involve primarily the cardiovascular system. Hypotension caused by peripheral vasodilation may occur, necessitating decreasing the barbiturate dose or the administration of fluids and vasopressors to maintain blood pressure. A recent systematic review of the literature suggested that one of every four patients receiving barbiturate therapy will develop hypotension. Care should be taken to avoid extravasation of pentobarbital and thiopental solutions because severe tissue damage may occur. Barbiturates should be administered by continuous infusion through a central line dedicated for this purpose. The potential for barbiturates to induce the hepatic metabolism of concurrent medications should be also considered. In addition to hypotension resulting from its diuretic effect, a reversible acute renal dysfunction may occur in patients with previously normal renal function after long-term, large-dose administration, especially if the serum osmolality or serum sodium exceed 320 mOsm/ kg (mmol/kg) and 160 mEq/L (mmol/L), respectively. Results of this study indicated a higher risk of death within 2 weeks of enrollment (relative risk 1. Phenytoin dosing regimens for adults and pediatric patients include an intravenous loading dose of 15 to 20 and 10 to15 mg/kg, respectively, followed by a maintenance dose of 5 mg/kg/day. The merits of preventive anticonvulsant therapy in patients who have not had a seizure postinjury historically have been more controversial. The potential for thromoembolic events using this procoagulant must be considered as part of any cost versus benefit analysis in these patients. It was the opinion of the author that the literature does provide a degree of support for improvements in memory, attention, concentration, and mental processing in this patient subset, although results and study designs were highly variable for those investigations included in the analysis. Additionally, the timing of administration of these drugs is controversial; the potential for cardiovascular side effects in the face of uncertain benefit would indicate that these drugs should be reserved for the postacute phase of treatment. A major concern with their use is the potential to reduce systemic blood pressure. Furthermore, careful attention must be paid to the potential for a variety of electrolyte, mineral, and acid-base disturbances, coagulopathies, and infections by obtaining various laboratory tests on a daily basis initially. The intensity of monitoring will be a function of the relative degree of neurologic and hemodynamic stability of the patient in the hours and days following the neurologic insult. Biochemical, cellular, and molecular mechanisms of neuronal death and secondary brain injury in critical care. Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. Early onset of lipid peroxidation after human traumatic brain injury: a fatal limitation for the free radical scavenger pharmacological therapy? Relationship between apoE4 allele and excitatory amino acid levels after traumatic brain injury. Predicting survival using simple clinical variables: a case study in traumatic brain injury. Management of brain-injured patients by an evidence-based medicine protocol improves outcomes and decreases hospital charges. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. In: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury. A critical analysis of the role of the neurotrophic protein S100B in acute brain injury. Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. Optimal temperature for the management of severe traumatic brain injury: effect of hypothermia on intracranial pressure, systemic and intracranial hemodynamics, and metabolism. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7. Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology. Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. What is the safest way to prevent deep venous thrombosis and pulmonary embolism after head or spinal cord injury? How soon after surgery or injury can I anticoagulate my patients who develop deep venous thrombosis? Does following the recommendations in the Guidelines for the Management of Severe Traumatic Brain Injury make a difference in patient outcome? Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Pharmacological enhancement of cognitive and behavioral deficits after traumatic brain injury. Dopamine agonists are effective and, compared to L-dopa, associated with less risk of developing motor complications but more likely to cause psychiatric symptoms, such as hallucinations and impulse control disorders. Surgery is reserved for patients who require additional symptomatic relief or control of motor complications despite receiving medically optimized therapy. A higher incidence is reported among males, with a male-to-female ratio of up to 2:1. The hydroxyl free radical can cause lipid peroxidation, thereby damaging neuronal cell membranes. Lewy pathology has been proposed to develop in a predictable anatomic distribution within the parkinsonian brain. In advanced stages, Lewy pathology spreads to the cortex, and this may correlate with cognitive and additional behavior changes. The indirect pathway involves activation of striatal dopamine2 (D2) dopamine receptors (which are coupled to a guanosine triphosphate-binding protein that opens potassium channels to hyperpolarize neurons, thereby reducing the excitability of the neuron). Motor Symptoms the patient experiences decreased manual dexterity, difficulty arising from a seated position, diminished arm swing during ambulation, dysarthria (slurred speech), dysphagia (difficulty with swallowing), festinating gait (tendency to pass from a walking to a running pace), flexed posture (axial, upper/lower extremities), "freezing" at initiation of movement, hypomimia (reduced facial animation), hypophonia (reduced voice volume), and micrographia (diminution of handwritten letters/ symbols). Autonomic and Sensory Symptoms the patient experiences bladder and anal sphincter disturbances, constipation, diaphoresis, fatigue, olfactory disturbance, orthostatic blood pressure changes, pain, paresthesia, paroxysmal vascular flushing, seborrhea, sexual dysfunction, and sialorrhea (drooling). Mental Status Changes the patient experiences anxiety, apathy, bradyphrenia (slowness of thought processes), confusional state, dementia, depression, hallucinosis/psychosis (typically drug induced), and sleep disorders (excessive daytime sleepiness, insomnia, obstructive sleep apnea, and rapid eye movement sleep behavior disorder).
Functioning in a manner somewhat similar to that of the second mechanism erectile dysfunction 42 discount aurogra 100mg overnight delivery, the third mechanism of immune response involves a protein carrier that combines with the drug and then attaches to the cell membrane impotence for males purchase aurogra 100mg with visa. In addition erectile dysfunction pump hcpc aurogra 100 mg on line, there are several other immune-mediated mechanisms that have been identified impotent rage quotes purchase aurogra 100 mg free shipping. The production of autoantibodies to a spoiled membrane is a mechanism in which the offending drug alters the neutrophil membrane. This alteration induces the formation of autoantibodies (antibodies that attach directly to the neutrophil), which causes cellular destruction by the phagocytic system. High concentrations of -lactam antibiotics, carbamazepine, and valproic acid have been associated with inhibition of colony-forming units of granulocytes and macrophages. More recently, immunosuppressive regimens combining antithymocyte globulin, glucocorticoids, and cyclosporine are gaining favor. Clinical data suggest that there is no difference in survival achieved with the two treatments among patients followed for 6 years. Parity between the treatments will necessitate that clinicians individualize treatment decisions, while considering risk factors, economics, and quality of life. Finally, drug-induced apoptosis and direct toxicity for pluripotent or bipotent hematopoietic progenitor stem cells have also been associated with clozapine and ticlopidine, respectively. That mechanism involves an accumulation of drug to toxic concentrations in hypersensitive individuals. Researchers have shown with in vitro cell cultures that penicillin derivatives in high concentrations inhibit the growth of myeloid colony-forming units in patients recovering from drug-induced agranulocytosis. Antithyroid medications, such as propylthiouracil and methimazole, have been reported to cause agranulocytosis. The current incidence of this adverse effect is unknown, but early publications report agranulocytosis in approximately 0. The antibodies and drug form a complex in the serum, and the complex nonspecifically binds to the cell membrane. Following discontinuation of the drug, most cases of neutropenia resolve over time, and only symptomatic treatment. The only prospective, randomized trial to date did not confirm the benefit of these growth factors. The complex then attaches to the cell membrane, and antibody formation is stimulated. However, another study demonstrated no relationship between age or dose and the incidence of thionamide-induced agranulocytosis. Agranulocytosis most commonly occurs within 1 to 3 months from the initiation of ticlopidine. Removal of the drug is the best treatment option, with counts usually returning to normal within 2 to 4 weeks. The phenothiazine class of drugs is known to cause drug-induced agranulocytosis by the innocent bystander mechanism. The onset of phenothiazineinduced agranulocytosis is approximately 2 to 15 weeks after the initiation of therapy, with a peak onset between 3 and 4 weeks. Chlorpromazine also increases the loss of macromolecules from the intracellular pools that are essential for cellular replication. It is believed that toxic effects of the phenothiazines are not seen in all patients taking the medications because most patients have enough bone marrow reserve to overcome the toxic effects. The causes of drug-induced hemolytic anemia can be divided into two categories: immune or metabolic. Those in the first category may operate much like the process that leads to immunemediated agranulocytosis, or they can suppress regulator cells, which can lead to the production of autoantibodies. Patients with drug-induced hemolytic anemia can present with signs of intravascular or extravascular hemolysis. Symptoms of hemolytic anemia can include fatigue, malaise, pallor, and shortness of breath. Depending on the antigenic stimulus, immune hemolytic anemia is either classified as autoimmune, alloimmune, or drug-induced. The Coombs test begins with the antiglobulin serum, which is produced by injecting rabbits with preparations of human complement, crystallizable fragment (of immunoglobulin) (Fc), or immunoglobulins. The mechanisms that have been proposed to explain how drugs can induce immune hemolytic anemia are similar to the mechanisms that produce drug-induced agranulocytosis. The antibody attaches to the drug without direct interaction with the erythrocyte. The extravascular anemia that follows is usually caused by IgG, and generally complement is not activated. The anemia usually develops gradually over 7 to 10 days and reverses over a couple of weeks after the offending drug is discontinued. The penicillin and cephalosporin derivatives given in high doses are primarily associated with this type of immune reaction. Quinidine and phenacetin are the prototype drugs of this reaction, but many other drugs have been implicated, including quinine and several sulfonamides. Because of this low affinity, only a small amount of drug is needed to cause the reaction, and the direct Coombs test is positive for complement only. This type of mechanism is associated with acute intravascular hemolysis that can be severe, sometimes leading to hemoglobinuria and renal failure. Following discontinuation and clearance of the drug from the circulation, the direct Coombs test will become negative. Approximately 10% to 20% of patients receiving methyldopa will develop a positive Coombs test, usually within 6 to 12 months of initiating therapy. After the withdrawal of the drug, results of the Coombs test can remain positive for many months. In an effort to explain why patients have a positive result from a Coombs test and no hemolysis, Kelton demonstrated that methyldopa impairs the ability of these patients to remove antibody-sensitized cells. Procainamide has also been reported to cause a positive result on the indirect Coombs test and hemolytic anemia. Hemolytic anemia caused by drugs through the hapten/adsorption and autoimmune mechanisms tends to be slower in onset and mild to moderate in severity. Conversely, hemolysis prompted through the neoantigen mechanism (innocent bystander) phenomenon can have a sudden onset, lead to severe hemolysis, and result in renal failure. The treatment of druginduced immune hemolytic anemia includes the removal of the offending agent and supportive care. In severe cases, glucocorticoids can be helpful,69 but some practitioners have questioned their efficacy. Both homozygotes and heterozygotes can be symptomatic, but homozygotes tend to have the most severe cases. However, the dose required for hemolysis to occur is often less than prescribed quantities of the suspected drug. One case of drug-induced oxidative hemolytic anemia has been reported in a child when dapsone (an oxidizing agent) was transferred through the breast milk of the mother, who was taking the drug. No other therapy is usually necessary, as most cases of drug-induced oxidative hemolytic anemia are mild in severity. Patients with these enzyme deficiencies should be advised to avoid medications capable of inducing the hemolysis. Deficiencies in either vitamin B12 or folate are responsible for the impaired proliferation and maturation of hematopoietic cells, resulting in cell arrest and subsequent sequestration. Examination of peripheral blood shows an increase in the mean corpuscular hemoglobin concentration. Some patients can have a normal-appearing cell line, and the diagnosis must be made by measurement of vitamin B12 and folate concentrations.
In patients with severe symptoms erectile dysfunction which doctor to consult buy 100 mg aurogra with visa, 3% sodium chloride solution (possibly combined with furosemide) should initially be used to more rapidly correct the hyponatremia erectile dysfunction medicine buy cheap aurogra 100mg on line. Furosemide can be administered concurrently to enhance the serum sodium correction by increasing the excretion of water erectile dysfunction treatment chennai buy 100mg aurogra amex. Application of these principles to the treatment of patients with various forms of hypotonic hyponatremia is discussed in the following sections erectile dysfunction pill brands aurogra 100 mg free shipping. More accurate equations have recently been derived, but the benefits of this more complex approach relative to the approach outlined below remain to be determined. Finally, an appropriate infusion rate can be calculated for this infusion volume to control the rate of increase in the serum sodium concentration. For the serum sodium to increase after infusion of a solution of sodium chloride, the concentration of sodium in the infusate must exceed the sum of the sodium and potassium concentration in the urine to effect net-free water excretion. In this case use of isotonic sodium chloride carries the potential hazard of actually worsening hypona- 879 For example, consider the case of a 170 centimeter (5 feet 7 inch), 60 kilogram (132 pound), 66-year-old woman who presents with nausea, vertigo, and disorientation that have developed over the past several days. She was started on carbamazepine 10 days ago for the treatment of trigeminal neuralgia. This should be an adequate response to alleviate her current symptoms, decrease the risk of more severe symptoms, and minimize the risk of osmotic demyelination syndrome. In the presence of symptoms, the serum sodium should be increased by approximately 1. Serial physical examinations of the heart, lungs, and neurologic status should be performed several times over the initial 12 hours of hospitalization. The serum sodium concentration should be measured every 2 to 4 hours, and the urine osmolality, sodium, and potassium should be measured every 4 to 6 hours over the first day of therapy. The rate of administration of the infusate should then be adjusted to avoid exceeding a rise in the serum sodium greater than 12 mEq/L (greater than 12 mmol/L) per day. The combination of the adaptive decrease in intracellular osmolality and rapid increase in serum osmolality results in excessive movement of water out of the brain cells, intracellular volume depletion, and thereby an increased risk of osmotic demyelination syndrome. Treatment of these patients should include correction of the underlying condition, if possible. For example, consider the case of a 56-year-old woman who was started on hydrochlorothiazide 10 days ago for the treatment of hypertension. Today she presents with complaints of mild nausea and "feeling dizzy" when she stands up. The expected increase in the serum sodium concentration following infusion of 1 L of 0. Advantages of 3% sodium chloride include more rapid correction of serum sodium concentration and smaller infusion volumes. The disadvantage of 3% sodium chloride is a higher risk of exceeding maximum recommended rates of correction and causing osmotic demyelination syndrome. Because the overriding initial treatment goal is to restore effective circulating volume, it might be necessary to infuse 0. The infusion rate can then be decreased to 100 to 150 mL/h so that the serum sodium level increases by no more than 12 mEq/L (12 mmol/L) over the initial 24 hours. It is important to recognize that the rate of increase in the serum sodium concentration can substantially increase once hypovolemia has been corrected if infusion rates are not decreased. Ideally, the potential for this increase in correction rate is recognized prospectively and infusion rates are appropriately adjusted. If the serum sodium is observed to be increasing at a rate greater than 12 mEq/L (greater than 12 mmol/L) per day, the infusate should be changed to 0. The goal is to increase the daily solute intake and excretion to approximately 900 mOsm (900 mmol) per day. Because an average diet contains approximately 600 mOsm (600 mmol), 9 grams of sodium chloride would be required to increase the osmolar excretion to 900 mOsm/day (900 mmol/day) (each 1-g sodium chloride tablet contains 17 mmol of sodium and 17 mmol of chloride). Because extracellular volume expansion is an expected adverse effect, a loop diuretic should be administered concurrently to avoid pulmonary congestion and peripheral edema. Loop diuretics also enhance water excretion by limiting the formation of the medullary concentration gradient. This results in an increase in urine output and freewater excretion along with a decrease in urine osmolality and an increase in serum sodium. These positive outcomes are achieved without significantly increasing the excretion of electrolytes and thus these agents have been called "aquaretics. Because it is available only for intravenous administration and is not approved for use in patients with heart failure, its utility for the treatment of chronic hyponatremia is very limited. Several selective V2 antagonists have been investigated recently and show promise for the treatment of several chronic hyponatremic syndromes. The serum sodium concentration should be measured every 2 to 4 hours to allow timely adjustment of the rate and composition of intravenous fluids to avoid an increase in the serum sodium greater than 12 mEq/L (greater than 12 mmol/L) per day. The goal is to induce negative water balance by restricting water intake to less than 1,000 to 1,200 mL/day, such that water losses from insensible sources (skin and lung) and from obligate urine and fecal losses exceed intake. Daily insensible water losses via skin and lungs are approximately 900 mL/day, whereas approximately 200 mL and a minimum of 500 mL/day is lost in stool and in urine output, respectively. Concomitant therapy with P-gp inhibitors and grapefruit juice has also been noted to result in increased serum concentrations. If, after 24 hours, a greater increase in serum sodium concentration is needed, the dosage may be increased to 30 mg once daily and after another 24 hours, to a maximum of 60 mg once daily. The vaptans have dramatic effects on water excretion and tolvaptan represents the greatest breakthrough in the therapy of hyponatremia and disorders of fluid homeostasis since the introduction of loop diuretics. It is important to recognize that vasopressin receptor antagonists are contraindicated in hypovolemic patients as their use would worsen the hypovolemia. A continued decline in the serum sodium level would indicate either nonadherence to the prescribed restriction or the need for a more stringent restriction. Once the serum sodium level has stabilized above 125 mEq/L (125 mmol/L), patients should then be seen every 2 to 4 weeks to assess neurologic status and to obtain serum and urine for sodium, potassium, and osmolality. This entails correction of the underlying cause when possible, as well as restriction of water intake to a volume less than 1,000 to 1,200 mL/day. This procedure can potentially exacerbate or precipitate hepatic encephalopathy, and should be avoided in patients with a history of encephalopathy. Vasopressin receptor antagonists have also been proposed for the treatment of hypervolemic hypotonic hyponatremia in patients with congestive heart failure and cirrhosis. Infants and comatose patients, as well as elderly or disabled patients with an impaired sensorium or functional status are therefore at highest risk for this disorder. Mortality from acute hypernatremia in children, which develops in less than 72 hours, ranges from 10% to 70%. In contrast, chronic hypernatremia in children, defined as that which develops over 3 or more days, has a mortality rate of 10%. Hypernatremia in adults is often associated with a serious underlying illness, which likely contributes to the high mortality rate. Patients develop hypovolemic, hypervolemic, or isovolemic hypernatremia depending on the relative magnitude of sodium and water loss or gain caused by the underlying condition. Water loss commonly occurs as a result of insensible losses (evaporative losses of water through the skin and lungs) in patients deprived of water. Hospitalized patients who are febrile or receiving mechanical ventilation are often treated with intravenous fluids containing insufficient free water to replace insensible losses. Hypernatremia can be observed in patients with hypotonic gastrointestinal losses (diarrhea or vomiting) or in patients who have been exposed to high temperatures who suffer large water losses from both sweat and insensible losses. This is typically iatrogenic, and can follow administration of sodium bicarbonate, use of hypertonic sodium chloride enemas, or intrauterine injection of hypertonic sodium chloride. The serum sodium concentration should be measured daily until it stabilizes above 125 mEq/L (125 mmol/L) following initiation of water restriction. Patients should then be assessed 1 week following discharge, and then every 2 to 4 weeks to assess compliance with the water restriction and other treatment measures, volume status, and hyponatremia-related symptoms. Hypernatremia results in movement of water from the intracellular space to the extracellular fluid. This increase in intracellular fluid tonicity then draws water into the neurons, thus limiting the decrease in cell volume.
Buy cheap aurogra 100mg line. Erectile Dysfunction | The Symptoms Signs & Causes.
Syndromes
Our method differs in that we also constrain paths between regions to follow tractography fibers instead of shortest paths between the two regions diabetes obesity and erectile dysfunction purchase 100 mg aurogra with visa. The logic is to attempt to follow actual connections rather than other shorter paths through the diffusion functions that have no physical reality impotence blood circulation discount aurogra 100mg without a prescription. In addition erectile dysfunction treatment diet discount aurogra 100mg with mastercard, we used the mean flow along the path instead of the minimum flow erectile dysfunction in diabetes treatment purchase 100 mg aurogra amex, to be more robust to noise in diffusion data. We describe how we preprocess our data to generate whole-brain tractography fibers running between 68 automatically parcellated regions of interest. In parallel, we compute a very dense lattice, or flow graph, from our diffusion data. We project the tractography fibers onto the dense flow graph to form projected paths connecting any two regions of interest. The paths are used to estimate flow between the regions of interest and generate a flow-based connectivity matrix. We compare these matrices to the standard connectivity matrices (based on counting fibers) using network measures and test how well they discriminate 70 between disease groups in our data. We discuss how inclusion of flow or capacity changes the network landscape of the brain. The graph shown (first panel) is downsampled for clarity; the true version is much denser. Next, fibers from a global probabilistic tractography algorithm are selected that connect two regions of interest. The projected path with the maximum mean flow is selected and we remove its mean flow from its edges in the graph. The maximum mean flow is added to the connectivity matrix and the process is repeated a set number of times. We projected fibers generated from tractography (parameterized polynomial curves) onto this lattice graph to find pathways in the lattice between different regions. The mean flow along these projected paths is used to estimate the relative rates of diffusion, or total integrated flow, between any pair of regions in the brain. Each node is connected to its surrounding voxels by edges (the 6 neighborhood around the voxel per node). We now compute a measure of the amount of flow passing between regions by finding paths between these regions as follows. The classic maximum flow problem has a variety of algorithms (Schrijver, 2002; Ford Jr et al. The Edmonds-Karp algorithm (Edmonds and Karp, 1972) is a widely used method to solve this problem. It works by finding a path between two regions in the graph, using breadth-first search, and subtracting the minimum flow along this path from the graph. The minimum flow or minimum edge constitutes the bottleneck along the path and represents the maximum flow along the path. This process is repeated with the updated graph until no more paths can be found between the two regions. The sum of the minimum flow edges from the paths is the maximum flow between the two regions. In this paper, we adapt the Edmonds-Karp method (Edmonds and Karp, 1972) to our diffusion data by restricting the paths to follow tractography fibers between the two regions. Our flow graph can have millions of nodes and edges, leading to an enormous number of possible paths between any two regions, but many of these may not be biologically plausible. Unlike prior methods, we restrict the paths to follow fibers from tractography and restrict our search to n paths per connection instead of all possible paths to estimate the flow in a practical amount of time. If we rely on the minimum flow along a path between two regions, it may falsely restrict the capacity of a path because of noise in our diffusion data (causing a single edge 74 along the path to be abnormally small). To remedy this, we compute the mean flow or mean edge weight along the path as an estimate of the passing flow. Tractography Fiber Projection We compute connections between two regions in the flow graph by following paths closest to tractography fibers connecting the two regions, and further select those fibers from our Hough tractography method that intersect the two regions of interest. These fibers are then projected into the flow graph by finding the closest nodes and edges along each fiber. This set of nodes and edges represents a projected path between the two regions in the flow graph. Flow Between Regions Paths between two regions of interest are then scored based on the their mean edge value or flow. We then select the path with the maximum mean flow and subtract its maximum mean flow from its edges in the flow graph. This modified graph is used to re-score the projected paths between the two regions and the process is repeated for a pre-specified number, n, of iterations. In our experiments, n = 10 was sufficient to capture the flow between all regions in our image. In addition, we computed standard fiber connectivity matrices that count the number of fibers connecting each region. The flow connectivity matrix may be thought of as a particular weighting of the fiber connectivity matrix from which it is derived. As is standard, ten different thresholds were applied to each connectivity matrix, to preserved 76 Table 4. The p-values are from two-sample t-tests and the threshold represents the proportion of weights preserved in the connectivity matrices before network measures are computed. Ten separate thresholds were applied to each connectivity matrix that preserved a proportion of the weights ranging from. For each of these matrices, we computed a total of fourteen (global efficiency, transitivity, path length, density, modularity, and small world were found both in weighted and binary matrices while mean degree and assortativity were found in only binary) different network measures at ten different weight preservation thresholds. The resulting measures were then used in two-sample t-tests comparing controls vs. We then analyzed the lowest p-value from each test to compare the discriminative ability of each network. We present here reo sults showing the utility of features derived only from brain connectivity in diffusion weighted images of the brain. The features we chose came from standard tractography fiber connectivity between regions and a novel flow based connectivity method. They used a technique to rank features and select the top features to use in a 10-fold cross-validation. Our method differs in that we use only measures of connectivity and use principal components analysis to reduce our feature set. Our results show a significant different in the accuracy of different features sets to distinguish between the two groups. This protocol was chosen after an effort to study trade-offs between spatial and angular resolution in a tolerable scan time (Jahanshad et al. The resulting images were segmented into 34 cortical regions (in each hemisphere) using FreeSurfer (Fischl et al. To generate close to 50, 000 fibers per subject, we used an accelerated form of this tractography method (Prasad et al. From these matrices we computed a set of network measures that quantify different network characteristics. We chose different subsets of these features in our experiments to understand the information they captured from the brain. Connectivity Matrix We compute connectivity matrices using two methods, the first is the relative frequency of fibers connecting regions, and the second is a novel method that computes flow between regions. Our first method takes fibers computed using the accelerated Hough tractography method and computes the number that intersect pairs of regions from the 68 cortical areas around the brain. The second method we used a flow based measure of connectivity between all region pairs (Prasad et al. In short, we first created a lattice network by connecting all lattice points (voxel centers) to all their neighbors.
References